Microbiology (2014), 160, 1007–1019
Review
DOI 10.1099/mic.0.076208-0
Physiological roles of small RNA molecules
Charlotte Michaux,13 Nicolas Verneuil,1 Axel Hartke1
and Jean-Christophe Giard2
Correspondence
Jean-Christophe Giard
1
[email protected]
2
Received 18 December 2013
Accepted 31 March 2014
Unité de Recherche Risques Microbiens (U2RM), Equipe Stress Virulence,
Université de Caen, 14032 Caen, France
Equipe Antibio-résistance, Université de Caen, 14032 Caen, France
Unlike proteins, RNA molecules have emerged lately as key players in regulation in bacteria. Most
reviews hitherto focused on the experimental and/or in silico methods used to identify genes
encoding small RNAs (sRNAs) or on the diverse mechanisms of these RNA regulators to
modulate expression of their targets. However, less is known about their biological functions and
their implications in various physiological responses. This review aims to compile what is known
presently about the diverse roles of sRNA transcripts in the regulation of metabolic processes, in
different growth conditions, in adaptation to stress and in microbial pathogenesis. Several recent
studies revealed that sRNA molecules are implicated in carbon metabolism and transport, amino
acid metabolism or metal sensing. Moreover, regulatory RNAs participate in cellular adaptation to
environmental changes, e.g. through quorum sensing systems or development of biofilms, and
analyses of several sRNAs under various physiological stresses and culture conditions have
already been performed. In addition, recent experiments performed with Gram-positive and Gramnegative pathogens showed that regulatory RNAs play important roles in microbial virulence and
during infection. The combined results show the diversity of regulation mechanisms and
physiological processes in which sRNA molecules are key actors.
Introduction
Small non-coding RNAs (sRNAs) occur in all kingdoms of
life and have become increasingly recognized as a novel
class of gene expression regulators. The eubacterial sRNAs,
known in bacteria since the early 1970s (typically, 50–
250 nt in length), generally do not contain expressible
ORFs, although some of them, such as SgrS or RNAIII of
Escherichia coli or Staphylococcus aureus, also contain coding
regions. However, only the success of recent systematic
genome-wide searches for genes encoding these molecules
has led to their full appreciation (Bradley et al., 2011;
Ferrara et al., 2012; Mraheil et al., 2010; Pellin et al., 2012;
Shioya et al., 2011; Silvaggi et al., 2006). Several screens
using various methods have increased the number of known
sRNAs (Pichon & Felden, 2008; Vogel & Sharma, 2005). In
E. coli, one of the best-studied models, the majority of the
expressed sRNAs are conserved in closely related pathogens,
such as Salmonella and Yersinia species (Hershberg et al.,
3Present address: Vogel lab, Institute for Molecular Infection Biology,
University of Würzburg, Germany.
Abbreviations: cRNA, CRISPR RNA; CRISPR, clustered regulatory
interspaced short palindromic repeat; PTS, phosphotransferase system;
RAP, RNAIII-activating protein; sRNA, small RNA; tmRNA, transfermessenger RNA; TRAP, target of RNAIII-activating protein; QS, quorum
sensing; VR-RNA, VirR-regulated RNA.
076208 Printed in Great Britain
2003). It has been estimated that enterobacterial genomes
with a mean size of 4–5 Mb might contain 200–300 sRNAs,
which correspond to ~5 % of the total number of genes
(Zhang et al., 2004). Substantial efforts have been made to
define sRNA functions in various physiological responses,
to identify their targets and the mechanisms by which they
affect them, and to analyse their integration into complex
regulatory networks in the cell (Richards & Vanderpool,
2011; Vogel & Wagner, 2007; Waters & Storz, 2009). With
regard to the regulatory mechanisms, sRNAs can be divided
into four main classes: RNAs modulating protein activity,
cis-encoded base-pairing RNAs, trans-encoded base-pairing
RNAs and CRISPRs (clustered regulatory interspaced short
palindromic repeats) (Storz et al., 2011). Cis-acting RNA
elements that are encoded on the DNA strand opposite the
target RNA share ¢75 nt complementarity with the mRNA
targets. Well-studied examples of these sRNAs are encoded
by genes located on mobile genetic elements such as those of
the toxin–antitoxin system involved in plasmid replication
control (Brantl, 2007; Fozo et al., 2008; Weaver, 2012).
Trans-encoded sRNAs share limited complementarities
with their mRNA targets and the chromosomal locations
of the corresponding genes are not correlated. Note that
usually the trans-acting sRNAs have more than one mRNA
target, contrarily to cis-acting sRNAs. Base-pairing between
the sRNA and its target mRNA usually leads to modification
Downloaded from www.microbiologyresearch.org by
IP: 88.99.165.207
On: Mon, 31 Jul 2017 20:23:17
1007
C. Michaux and others
of translation, mRNA degradation by the RNase or both
(Aiba, 2007; Gottesman, 2005). sRNAs modulating protein
activity are ‘non-base-pairing’ molecules. They can interact
directly with proteins and modify their activities by sequestration, e.g. csrB–csrC sRNA or 6S RNA in E. coli (Babitzke
& Romeo, 2007; Steuten et al., 2014; Wassarman, 2007).
Other non-base-pairing sRNAs, such as RNase P, 4.5S
or transfer-messenger RNA (tmRNA), are involved in the
regulation of proteins (Herskovits et al., 2000; Lai et al.,
2010; Moore & Sauer, 2007). As an example, the wellknown tmRNA is involved in translational surveillance
and ribosome rescue. The last discovered regulatory RNA
class comprises the CRISPR sequences, highly variable
DNA regions of 24–47 bp that consist of a ~550 bp leader
sequence followed by a series of 2–249 repeat-spacer units
called CRISPR RNA (crRNA) which provide resistance to
bacteriophages and prevent plasmid conjugation. crRNAs
appear to target foreign DNAs and allow their degradation
(Richter et al., 2012; Sorek et al., 2008).
The various biological roles of sRNA elements encompass
the regulation of metabolism, growth processes or adaptation to stress. Moreover, recent evidence shows that
regulatory RNAs play key roles in microbial pathogenesis
(Gong et al., 2011; Koo et al., 2011; Toledo-Arana et al.,
2007; Vogel, 2009; Waters & Storz, 2009). During infection,
bacterial pathogens have to adapt rapidly to changing
environmental conditions in the host, including survival
strategies in specific niches, avoidance of exposure to the
immune system and systemic toxicity. Among the multiple
infectious strategies that bacterial pathogens have developed, regulatory RNAs are considered as signal transducers
of environmental cues by participating in the precise
coordination of gene expression. Several sRNAs have been
shown to regulate the synthesis of virulence factors and
other pathogenic traits by adapting the bacterial metabolism in response to the host.
Many reviews deal with the mechanism by which sRNAs
interact with their target or experimental procedures leading
to the identification of many sRNAs, although only a small
proportion of them have been analysed at the functional
level (Altuvia, 2007; Gottesman & Storz, 2011; Gottesman,
2005; Mraheil et al., 2010; Sharma & Vogel, 2009; Storz et al.,
2011; Vogel & Wagner, 2007; Waters & Storz, 2009). Thus,
here, we review examples of sRNAs that are involved in
numerous cellular processes, such as energy metabolism,
quorum sensing (QS) and biofilm formation, stress response
and adaptation to growth conditions, and pathogenesis.
We concentrate on the functional aspects of those sRNA
molecules corresponding to transcripts that interact with
mRNA or protein targets. The regulatory RNAs, such as
riboswitches, attenuators, thermosensitive stem–loop structures in the untranslated region and the CRISPR, reviewed
extensively elsewhere (Barrangou, 2013; Waters & Storz,
2009; Winkler & Breaker, 2005), will not be presented here.
This review aims to illustrate the diversity of physiological
characteristics where sRNAs are key regulators and their
importance in cell behaviour.
1008
sRNA and cellular metabolism
Carbon metabolism
Many bacteria alternate periods of nutrient abundance
and famine. These changes trigger major switches in gene
expression and require coordination of global regulatory
networks. These fine orchestrations that depend on the
nature and the quantity of nutrients usually implicate
specific transcriptional regulators and RNA regulators.
Recently, some studies showed that sRNA molecules can
regulate the expression of other regulators (Table 1). One
of them, the Csr (carbon storage regulator) system, ensures
connections between carbon metabolism and various other
traits in many bacteria. In E. coli, the central component of
this system is the repressor CsrA, which is known to be the
regulator of carbon starvation and glycogen biosynthesis,
mobility, QS, acetate metabolism, and flagellum biosynthesis, and more recently it has been identified to play
a prominent role in the virulence of numerous bacteria
(Heroven et al., 2012; Romeo et al., 2013). Two sRNAs,
CsrB (369 nt) and CsrC (242 nt), antagonize the activity of
CsrA during the exponential growth phase and repress
metabolic pathways related to the stationary phase (Babitzke
& Romeo, 2007; Revelles et al., 2013).
CsrA-like proteins are called RsmA and RsmE in Pseudomonas and Erwinia species, respectively, where they also
play a crucial role in virulence (Lapouge et al., 2008). In
Pseudomonas aeruginosa, two sRNAs, RsmY and RsmZ,
sequester the translational regulator RsmA (González et al.,
2008). Note that the overexpression of RsmZ has significant effects on the synthesis of several exoproducts,
as observed for the RsmA mutant strain (Heurlier et al.,
2004).
Sugar utilization is a key step in bacterial cell life and cellular
adaptations are frequently needed according to the energy
source available in the environment. Bacterial phosphoenolpyruvate carbohydrate phosphotransferase systems
(PTSs) mediate the uptake of sugars and their concomitant
phosphorylation (Deutscher et al., 2006). In E. coli, the main
PTS importing glucose contains the transporter PtsG,
generating glucose 6-phosphate in the presence of glucose.
This phosphosugar, which is toxic if it accumulates inside
cells, causes the phenomenon known as ‘phosphosugar
stress’ (Morita et al., 2004). This leads to the activation of
SgrR, a transcriptional activator and main coordinator of
the response to glucose-phosphate stress, and the synthesis
of the SgrS sRNA, responsible for the ptsG mRNA degradation reducing further accumulation of glucose 6-phosphate (Papenfort et al., 2013; Vanderpool & Gottesman,
2004; Zhang et al., 2003). The data were confirmed by the
analysis of the sgrS mutant and its growth defect under
phosphosugar stress conditions (Morita et al., 2006).
The sRNA Spot42 is another illustration of the role of a
small transcript in the control of sugar metabolism. The
E. coli galETKM operon encodes enzymes that convert
galactose to the glycolytic intermediate glucose 1-phosphate.
The galactokinase activity of GalK depends on the presence
Downloaded from www.microbiologyresearch.org by
IP: 88.99.165.207
On: Mon, 31 Jul 2017 20:23:17
Microbiology 160
http://mic.sgmjournals.org
Table 1. Physiological roles of sRNA in various bacterial species
Role of sRNA/species
Cellular metabolism
Carbon metabolism
Escherichia coli
sRNA
Main targets
Partners
SgrS
ptsG
Spot42
galK
Hfq, SgrR,
RNase E, Eno
Hfq
CsrB–CsrC
CsrA
CsrD, RNase E,
GlmY–GlmZ
glmS
Hfq, YhbJ
Pseudomonas aeruginosa
RsmY–RsmZ
rsmA
PNPase
Amino acid metabolism
E. coli
GcvB
oppA, dppA, ssT
GcvA, GcvR, Hfq
Sr1
ahrC
CcpA, CcpN
RyhB
P. aeruginosa
PrrF1–2
bfr, sdh, sodB
Fur, Hfq,
RNase E/III
QS and biofilm formation
Vibrio cholerae
Qrr1–5
hapR/aphA
Hfq
Staphylococcus aureus
RNAIII
mRNAs of QS
RAP/TRAP
E. coli
CsrB/C
CsrA
McaS
flhDC
MicA
ompA
sE
References
Responsible for ptsG degradation,
a consequence of glucose 6-phosphate reduction
Prevents the translation of the galK operon,
converting galactose in glucose 1-phosphate
Represses the carbon storage regulator CsrA
and impacts metabolic pathways
Involved in cellular response to DNA damage,
in addition to allowing glmS activation
Antagonizes the effect of the CsrA-like protein
RsmA on swarming mobility or lipase production
Vanderpool & Gottesman (2004)
Represses peptide transporters, induced by high
glycine levels and enhances bacterial survival
under acid pH via RpoS regulation
Controls the AhrC transcriptional activator of
the two operons encoding catabolic and transport
enzymes for arginine catabolism, and stimulated
by L-arginine and the stationary phase
Jin et al. (2009);
Pulvermacher et al. (2009)
Leads to the rapid degradation of iron-binding
mRNAs; RyhB also activates some mRNAs
Leads to the rapid degradation of
iron-binding mRNAs
Massé & Gottesman (2002);
Sorger-Domenigg et al. (2007)
Wilderman et al. (2004)
Promotes the translation of genes required for
virulence and biofilm formation, and affects at least
four mRNAs (luxO/U, hapR, aphA and vca0939)
Represses expression genes encoding cell adhesion
proteins, and induces expression of genes encoding
toxins and other virulence factors
Activates flhDC, the regulator of flagella expression,
and represses pga, involved in the expression of a
biofilm matrix component
Activates the flhDC operon and CsrA, a negative
regulator of pgaA translation
Represses various porins, such as ompA, and its
expression is essential for proper biofilm formation
Hammer & Bassler (2007)
1009
Downloaded from www.microbiologyresearch.org by
IP: 88.99.165.207
On: Mon, 31 Jul 2017 20:23:17
Beisel & Storz (2011)
Babitzke & Romeo (2007);
Modi et al. (2011)
González et al. (2008)
Heidrich et al. (2006, 2007)
Korem et al. (2005)
Mika & Hengge (2013)
Jørgensen et al. (2013)
Kint et al. (2010);
Mika & Hengge (2013)
Roles of sRNAs
Iron regulation
E. coli
Remarks
Role of sRNA/species
sRNA
Main targets
Stress response and adaptation to growth conditions
Acid stress response
E. coli
GadY
gadXW
Partners
Remarks
RNase III
Acts as a positive regulator of the gadXW operon
where gadX encodes the major acid tolerance regulator
Regulates PspF transcription which leads to
altered cell survival at high pH
References
Opdyke et al. (2011)
6S RNA
pspF
Oxidative stress response
E. coli
OxyS
rpoS, fhlA
Hfq
Acts as an antimutator, inhibits rpoS translation, regulates
fhlA, activator of the hyp operon and contributes to cell
protection against oxidative DNA damage
Altuvia et al. (1997);
Johnson et al. (2006)
Osmotic stress
E. coli
FnrS
sodB, maeA,
gpmA, folEX
Hfq
Durand & Storz (2010)
ArcZ
arcB
Expressed under anaerobic conditions; under the
control of two O2-dependent FNR and ArcA regulators,
downregulates mRNAs encoding enzymes of energy
metabolism
Under aerobic conditions, inhibits arcA by
downregulation of arcB
Regulates the expression of the major outer
membrane porin OmpF
Represses genes encoding outer membrane
proteins cirA, fecA, fepA and ompT
Facilitates omp mRNA decay as part of the
envelope stress response
Stimulates RpoS synthesis in an osmolarity-dependent
manner in response to cell envelope stress
Andersen & Delihas (1990)
Aerobic or anaerobic growth conditions
E. coli
MicF
ompF
Trotochaud & Wassarman
(2006)
Mandin & Gottesman (2010)
Microbiology 160
OmrA/OmrB
Four porins
Hfq
RybB
omp mRNA
sE
RprA
rpoS
Hfq
Phosphosugar stress
E. coli
SgrS
ptsG, manXYZ, yigL
Decreases phosphosugar accumulation by repressing
translation of sugar transporter mRNA and
enhancing translation of sugar phosphatase mRNA
Papenfort et al. (2013);
Rice & Vanderpool (2011)
Pathogenesis
Staphylococcus aureus
RNAIII
hla, prot A,
coagulase, rot
Boisset et al. (2007)
Streptococcus pyogenes
FasX
fasBCA
Clostridium perfringens
VR-RNA
colA/plc
Effector of the agr operon; activates hla translation
encoding haemolysin and represses the synthesis of
major cell surface virulence factors, such as coagulase,
protein A and the transcriptional regulator rot
Regulates the fasBCA regulon required for the
repression of adhesins FBP54 and MRP, and for the
activation of virulence factors such as streptokinase
Under the dependence of VirRS system; responsible
for the regulation of toxin genes, such as k-toxin
(colA) and a-toxin(plc)
Downloaded from www.microbiologyresearch.org by
IP: 88.99.165.207
On: Mon, 31 Jul 2017 20:23:17
Guillier et al. (2006)
Majdalani et al. (2002)
Madhugiri et al. (2010)
Kreikemeyer et al. (2001)
Shimizu et al. (2002)
C. Michaux and others
1010
Table 1. cont.
Grieshaber et al. (2006)
Heurlier et al. (2004)
Mraheil et al. (2010, 2011)
Roberts & Scott (2007)
Mangold et al. (2004)
Hc1
Hfq
chiA
RsmA
rivR
mga
Regulates virulence factors at transcriptional
(emm and sic, respectively, encoding surface-exposed
virulence M protein and inhibitor of the complement
system) and post-transcriptional levels (SpeD cysteine
protease)
Activates a trans-acting RNA, mga operon,
implicated in the expression of virulence genes
such as scpA, sic, fba and scl1
Acts as a post-transcriptional regulator of the
chitinase ChiA
Activated by the GacAS system; prevents RsmA
(regulator of genes important for virulence
and survival) activity by sequestration
Acts indirectly as an activator by impeding the
synthesis of the histone Hc1, required for
bacterial differentiation in the infection process
emm, sic, SpeD
Main targets
Partners
Remarks
References
Roles of sRNAs
of glucose and the 109 nt Spot42 sRNA (Beisel & Storz,
2011; Beisel et al., 2012). Indeed, Spot42 specifically binds to
the 59 part of the galK mRNA and prevents translation of the
galK operon.
Amino acid metabolism
Amino acids may also be used as energy sources by bacteria
and some published results showed that the regulation of
their catabolism can involve sRNA. In Bacillus subtilis, the
use of arginine requires the products of the rocABC and
rocDEF operons encoding catabolic and transport enzymes.
RocR, which negatively regulates its own synthesis, and
AhrC, controlled by the sRNA Sr1, are both transcriptional
activators of rocABC and rocDEF (Gardan et al., 1997;
Heidrich et al., 2006). The interaction between Sr1 and ahrC
mRNA prevents the assembly of a translation initiation
complex (Heidrich et al., 2006, 2007). Sr1 transcription is
stimulated by the presence of L-arginine or stationary-phase
entrance and is repressed when sugars are used as the energy
source (Heidrich et al., 2007).
Another sRNA involved in the regulation of amino acid
catabolism is the 206 nt sRNA GcvB of Salmonella enterica
sv. Typhimurium, induced by high concentrations of glycine
and activated by GcvA, a regulator known to activate the
gcvTHP glycine degradation operon. GcvB regulates oppA
and dppA mRNAs, which encode oligopeptide and dipeptide
periplasmic binding proteins, respectively (Pulvermacher
et al., 2009; Urbanowski et al., 2000). They also repress
directly transcripts encoding proteins implicated in peptide
transport as well as permeases in E. coli (Sharma et al., 2007).
In addition, in Salmonella, as in E. coli, the mRNAs encoding
amino acid transporters are GcvB targets (Kim et al., 2002;
Ogawa et al., 1998; Sharma et al., 2007, 2011). Interestingly,
experiments using an E. coli strain lacking GcvB sRNA
showed that this sRNA enhances the ability of bacteria to
survive acid pH. This is explained by the upregulation of the
level of the alternative sigma factor RpoS (Jin et al., 2009).
Such results point out the interconnection between energy
metabolism and the bacterial stress response in which sRNA
molecules can play a role.
http://mic.sgmjournals.org
RsmY–RsmZ
IhtA
P. aeruginosa
Chlamydia trachomatis
LhrA
Listeria monocytogenes
RivX
Pel
Role of sRNA/species
Table 1. cont.
sRNA
Iron regulation
In E. coli, the sRNA RyhB is a key player for adaptation to
iron-limiting conditions. It redirects cellular iron use by
preventing new resynthesis of non-essential iron-containing enzymes (an effect called ‘iron sparing’) and enhancing
the ability of cells to synthesize iron-scavenging siderophores (Richards & Vanderpool, 2011). Indeed, RyhB
is known to base-pair with at least 18 transcripts (encoding
56 proteins mainly involved in iron metabolism), some of
which encode iron-binding proteins such as sodB (encoding iron superoxide dismutase), leading to rapid degradation of the transcripts (Massé & Gottesman, 2002; Massé
et al., 2003, 2007). The result of destroying the mRNA (and
therefore stopping synthesis of these iron-binding proteins)
is a decrease of the cellular requirement for iron, which
Downloaded from www.microbiologyresearch.org by
IP: 88.99.165.207
On: Mon, 31 Jul 2017 20:23:17
1011
C. Michaux and others
makes more iron available for essential proteins. Moreover,
physiological studies revealed that a RyhB mutant strain has a
significant delay in growth, is defective in both biofilm
formation and chemotaxis, and produces significantly less
enterobactin than WT cells under conditions of iron starvation (Jacques et al., 2006; Mey et al., 2005; Salvail et al.,
2010). sRNAs with similar functions have been identified in
different Gram-negative species, such as PrrF1 and PrrF2 of
P. aeruginosa. In E. coli and P. aeruginosa, the production
of sRNA associated with iron assimilation is regulated by
the Fur repressor when iron is bound to it. Under iron
limitation, the sRNA is transcribed and consequently reduces
synthesis of iron-binding proteins, but can also repress the
synthesis of its own regulator Fur (Vecerek et al., 2007).
Role of sRNA in QS and biofilm formation
QS is a form of cell communication in bacteria that provides
information about the population density, leading to genetic
changes allowing in some cases biofilm formation (Waters &
Bassler, 2005). It is becoming apparent that integration of
information by QS systems is regulated by sRNA molecules
(Table 1). sRNAs described in the following examples
illustrate how such molecules can be involved in different
aspects of cellular physiology, such as the stress response,
virulence and energy metabolism.
Vibrio cholerae synthesizes and responds to autoinducers
with two-component membrane-bound sensor kinases as
receptors (Miller et al., 2002). Each sensor transfers information into the phosphorelay protein LuxU, which subsequently transmits the signal to the response regulator
protein LuxO (Bassler et al., 1994; Freeman & Bassler, 1999;
Lilley & Bassler, 2000). Depending on the cell density,
LuxU or LuxO is phosphorylated and Vibrio QS genes are
expressed. At low cell density, LuxO is phosphorylated and
can activate the transcription of five non-coding quorumregulated sRNAs (qrr1–5) that are functionally redundant
(Bardill et al., 2011). Qrrs repress their own regulator LuxO
(Svenningsen et al., 2009) and inhibit the translation of
three other targets, all involved in the global regulation of
V. cholerae pathogenicity: hapR (encoding the transcription
factor that represses virulence genes) (Lenz et al., 2004),
aphA (encoding the transcriptional factor that enhances
virulence gene expression) (Rutherford et al., 2011) and
vca0939 (encoding a protein stimulating biofilm formation)
(Hammer & Bassler, 2007). Note that, at high cell density,
accumulation of autoinducers causes the dephosphorylation
of LuxO which cannot further activate transcription of Qrrs.
In Staphylococcus aureus, one QS system involves the
sRNA RNAIII, which plays an important role in virulence,
demonstrating the pivotal role a sRNA can play in diverse
parts of bacterial physiology. This micro-organism uses the
peptide RNAIII-activating protein (RAP) and its target
molecule TRAP as autoinducers, detected by two-component associated membrane sensor kinases that phosphorylate
the cognate cytoplasmic response regulators (Lyon & Novick,
2004). At high cell density, binding of the autoinducing
1012
peptide triggers expression of the regulatory RNA RNAIII.
This RNAIII represses expression of genes encoding cell
adhesion proteins important for early colonization stages,
and induces expression of genes encoding several toxins,
exoproteins and other virulence factors (Johansson &
Cossart, 2003; Korem et al., 2005; Toledo-Arana et al.,
2007) (see ‘Role of sRNA in pathogenesis’ below).
As mentioned above, QS is used as a signal for the cell to
form biofilms, which represent the prevalent microbial mode
of existence in nature (Flemming & Wingender, 2010). Such
structures confer protection against environmental stresses
as well as antibiotics and play critical roles in microbial
pathogenesis. In addition, the formation of biofilms (switching from the planktonic to the surface-associated mode of
growth) requires complex regulatory cascades. In E. coli, the
two sRNAs CsrB and CsrC (already known to interact with
CsrA, see ‘sRNA and cellular metabolism’ above) activate
FlhDC (encoding a flagellar master regulator) and downregulate the expression of the pga operon, encoding a polyN-acetyl-D-glucosamine extracellular matrix, one of the
biofilm components (Mika & Hengge, 2013).
Multiple other sRNAs have been identified, modulating
the expression or activity of transcriptional regulators and
components of regulatory networks required for attachment
and biofilm formation, and also linked to the stress response
or metabolism (Mika & Hengge, 2013; Romeo et al., 1993).
Among them, McaS (multicellular adhesive sRNA) and MicA
(regulator of ompA mRNA) have important roles in adhesion
and motility, respectively. McaS activates directly the flhDC
mRNA, but also activates synthesis of the exopolysaccharide
b-1,6-N-acetyl-D-glucosamine by binding the global RNAbinding protein CsrA, a negative regulator of pgaA translation
(Jørgensen et al., 2013; Thomason et al., 2012). MicA, whose
overexpression increases motility in soft agar plates, downregulates the expression of several outer membrane porins in
E. coli and Salmonella (De Lay & Gottesman, 2012).
Role of sRNA in the stress response and in
adaptation to growth conditions
Some sRNA functions in various physiological responses
have already been identified, more particularly concerning
adaptation of bacteria to chemical stresses and varying
culture conditions. Generally, the expression of sRNAs is
regulated tightly and induced by specific environmental
conditions. The involvement of sRNA in the stress response
is closely related to microbial pathogenesis as cells have to
cope with stresses during the infection process (i.e. body
fluids, phagocytosis and immune response). Here, examples are given to underscore the role of sRNA in acid,
oxidative or osmolarity stress, and adaptation to grow
under aerobic or anaerobic conditions (Table 1).
sRNA and the acid stress response
One of the main defences of E. coli against extreme acid pH
is the induction of two glutamate decarboxylase enzymes,
Downloaded from www.microbiologyresearch.org by
IP: 88.99.165.207
On: Mon, 31 Jul 2017 20:23:17
Microbiology 160
Roles of sRNAs
GadA and GadB (Castanie-Cornet et al., 1999). Glutamate
is transformed to c-aminobutyric acid by these enzymes, a
process that consumes intracellular protons (Homola &
Dekker, 1967). Expression of GadA and GadB is under
the control of GadX, the major acid tolerance regulator,
present in a bicistronic operon structure with gadW
(Tramonti et al., 2002). The GadY sRNA overlaps the 39
end of the gadX, acting as a positive regulator of acid stress
response genes by base-pairing to the gadXW mRNA,
and contributes to separate and stabilize the bicistronic
transcript (Opdyke et al., 2004).
sRNA and the oxidative stress response
In E. coli and closely related bacteria, OxyR regulates
numerous genes whose expression is induced by hydrogen
peroxide and defends the bacteria against peroxides. OxyS
(a 109 nt sRNA) is part of the OxyR regulon, which acts as a
regulator involved in the adaptation to hydrogen peroxide
and helps to protect cells against oxidative damage (Altuvia
et al., 1997). It is also described as a regulator of at least 40
genes in E. coli, including fhlA encoding an activator of the
formate–hydrogen lyase complex expressed in the presence
of formate, and the hyp operon encoding accessory proteins
essential for the maturation of the [NiFe] hydrogenase
enzymes, as well as rpoS encoding the ‘general stress sigma
factor’ RpoS (Altuvia et al., 1997, 1998; Zhang et al., 1998).
Note that inactivation of oxyRS in the WT strain significantly increased its susceptibility to hydrogen peroxide
and attenuated its virulence in a mouse model (Johnson
et al., 2006).
sRNA and the osmotic stress response
Depending on the osmolarity, the OmpR regulator modulates the transcription of the two most abundant outer
membrane proteins in E. coli, OmpF and OmpC, in
different ways. In addition to this regulation, MicF, the
first base-pairing RNA discovered in the E. coli genome,
was shown to regulate the expression of the porin OmpF
(Andersen & Delihas, 1990; Coyer et al., 1990). Expression
of MicF RNA is regulated by multiple signals, and is
essential for osmoregulation at low and medium levels of
osmolarity. At higher osmolarity, the role of MicF RNA
is masked by the strong transcriptional osmoregulation
exerted by OmpR (Ramani et al., 1994). Five additional
sRNAs, MicC, MicA, RyhB, RseX and IpeX, modulators
of expression of the most abundant outer membrane
porins, OmpA, OmpC and OmpF, have also been identified
and reviewed by Guillier et al. (2006). Additional outer
membrane proteins are capable of acting as channels and
are also subject to post-transcriptional regulation by sRNAs.
The OmrA (88 nt) and OmrB (82 nt) sRNA loci are located
in the same intergenic region, induced by high osmolarity
and regulated by the OmpR response regulator (Guillier
et al., 2006; Wassarman et al., 2001; Zhang et al., 2003).
Whole-genome expression analysis after overproduction
of either OmrA or OmrB indicated that these two sRNAs
http://mic.sgmjournals.org
mainly negatively regulate the expression of several genes
encoding multiple outer membrane proteins, including
cirA, fecA, fepA and ompT (Guillier et al., 2006). Lastly,
RybB, an 80 nt sRNA under control of sE, targets a large set
of porins and facilitates omp mRNA decay as part of the
envelope stress response (Papenfort et al., 2006). Characterization of a DrybB mutant showed that its better
resistance to cell envelope stress seems to be due to the
upregulation of sE (Hobbs et al., 2010).
In E. coli, the 105 nt regulatory sRNA RprA (RpoS regulatory RNA A) stimulates RpoS synthesis by base-pairing in an
osmolarity-dependent manner in response to cell envelope
stress (Majdalani et al., 2002). Transcription of RprA is
regulated by the RcsC/RcsB phosphorelay system, found
previously to regulate capsule synthesis and the activity
of the promoter of ftsZ, the cell division gene. Note that
another study has shown that the osmolarity-dependent
turnover of RprA contributes to its own abundance
(Majdalani et al., 2002).
sRNA and aerobic or anaerobic growth conditions
E. coli is able to grow under both aerobic and anaerobic
environments. Shifts between low and high oxygen concentrations induce profound changes in gene expression
(Constantinidou et al., 2006; Kang et al., 2005; Salmon et al.,
2003). Two transcriptional regulators, FNR (fumarate and
nitrate reduction) and ArcA (aerobic respiratory control),
whose activities are modulated by oxygen availability, impact
many of the changes in gene expression associated with
a transition from aerobic to anaerobic metabolism. FNR,
only active under anaerobic conditions, is a direct sensor
of oxygen. The sRNA FnrS, whose expression is induced
by anaerobic conditions in an FNR- and ArcA-dependent
manner, downregulates at least 32 mRNAs, many of which
encode enzymes involved directly in energy metabolism,
such as maeA (malate dehydrogenase), gpmA (phosphoglycerate mutase), folE (GTP cyclohydrolase), folX (dihydroneopterin triphosphate epimerase) or sodB (superoxide
dismutase) (Durand & Storz, 2010). ArcA is the cytosolic
response regulator of a two-component system, in which
ArcB is the transmembrane histidine kinase sensor
(Georgellis et al., 2001). The sRNA ArcZ, which interacts
with arcB, is produced under aerobic growth or repressed
under anaerobic conditions (Mandin & Gottesman, 2010).
ArcZ regulates RdaR morphotype (multicellular behaviour
of Salmonella enterica and E. coli, characterized by the
expression of the adhesive extracellular matrix components
cellulose and curli fimbriae), and also the transition between
sessility and mobility (Monteiro et al., 2012).
Role of sRNA in pathogenesis
As sRNAs participate in the genetic regulation of cellular
metabolism, biofilm formation and the stress response of
Gram-positive and Gram-negative pathogens, they have an
impact on the pathogens’ ability to persist and consequently
Downloaded from www.microbiologyresearch.org by
IP: 88.99.165.207
On: Mon, 31 Jul 2017 20:23:17
1013
C. Michaux and others
on their pathogenicity. In addition to this, several studies
have identified sRNAs that regulate specifically the expression of virulence factors (Table 1). In the following sections,
several examples of such sRNAs are presented from various
bacterial species. These works increase our knowledge of the
mechanisms of the bacterial infection process, and open a
new research path towards innovative therapeutic strategies
and new diagnostic tools (Mraheil et al., 2010).
sRNA in the pathogenesis of Staphylococcus aureus
As mentioned in the QS systems section above, in Staphylococcus aureus the sRNA RNAIII acts as a sensor of
population density and is required for virulence in animal
models (Cheung et al., 1994; Gillaspy et al., 1995; Novick &
Geisinger, 2008; Novick & Muir, 1999; Novick, 2003).
RNAIII controls the switch between the early expression of
surface proteins and the late expression of exotoxins, but it
also encodes a 26 aa d-haemolysin peptide (Novick et al.,
1993; Waters & Storz, 2009). The 59 domain of RNAIII
activates translation of hla mRNA encoding a-haemolysin
(Morfeldt et al., 1995; Novick et al., 1993), and the 39 end
and the central domain of this sRNA repress the synthesis of
major cell surface virulence factors (protein A, coagulase,
fibrinogen-binding protein) as well as the transcriptional
regulator Rot. By repressing the synthesis of Rot, RNAIII
also induces many downstream effects and activates
indirectly the synthesis of many exotoxins (Boisset et al.,
2007; Huntzinger et al., 2005; Morfeldt et al., 1995). Using a
DRNAIII deletion mutant strain, the role of the sRNA in
adherence to host tissues was studied. The study showed
that RNAIII downregulated Staphylococcus aureus adherence to fibrinogen and upregulated adherence to fibronectin
and endothelial cells (Shenkman et al., 2002).
co-expressed with the downstream gene encoding the
response regulator RivR and was shown to affect positively
the transcription of members of the Mga regulon, e.g. scpA
(peptidase), sic (streptococcal inhibitor of complement) and
fba (fibronectin-binding protein) or scl1 (a collagen-like
protein) (Leday et al., 2008; Roberts & Scott, 2007).
sRNA in the pathogenesis of Clostridium perfringens
The sRNA VR-RNA (VirR-regulated RNA) of Clostridium
perfringens is positively regulated by the two-component
VirR/VirS system, which controls (positively and negatively) the level of many virulence factors sloping letter
theta-toxin (perfringolysin O), k-toxin (collagenase), atoxin (phospholipase C), sialidase, protease and haemagglutinin] (Lyristis et al., 1994). Moreover, study of the VRRNA mutant revealed the positive effect of this sRNA in the
regulation of toxin genes such as plc (a-toxin), ptp (protein
tyrosine phosphatase), cpd (nucleotide phosphodiesterase),
ycgJ, metB, cysK and ygaG (genes coding for other toxins),
and colA (k-toxin) (Awad et al., 2000; Obana et al., 2013;
Ohtani et al., 2003; Podkaminski & Vogel, 2010).
sRNA in the pathogenesis of Listeria monocytogenes
The LhrA sRNA of L. monocytogenes acts as a post-transcriptional negative regulator of chiA (encoding chitinase).
chiA contributes to the pathogenesis of L. monocytogenes
in the mouse model, possibly through the recognition of
glycoproteins or other carbohydrate moieties present in the
infected host. Their expression depends on at least two
regulatory proteins: the central virulence regulator PrfA
and the alternative stress sigma factor sB (Mraheil et al.,
2010, 2011).
sRNA in the pathogenesis of Streptococcus pyogenes
sRNA in the pathogenesis of Pseudomonas aeruginosa
In some other Gram-positive pathogens, several sRNAs have
been shown to interact with the expression of transcriptional
regulators or proteins clearly involved in the virulence of the
bacteria. In Streptococcus pyogenes, three sRNAs participate
in the control of virulence factor expression. FasX RNA is
part of an operon encoding two histidine kinases (FasBC)
and one response regulator (FasA) (Kreikemeyer et al., 2001).
The fasBCA regulon, via FasX RNA, negatively controls the
expression of two matrix protein-binding adhesins (fibronectin-binding proteins FBP54 and MRP) and has a positive
influence on the activities of two secreted virulence factors
(streptokinase and streptolysin S) (Kreikemeyer et al., 2001).
FasX also controls the interaction of Streptococcus pyogenes
with epithelial laryngeal cells (Klenk et al., 2005). The second
sRNA, Pel, acts as a regulator of virulence factor expression,
e.g. emm (encoding the surface-exposed virulence M protein),
sic (encoding a streptococcal inhibitor of the complement
system) and speB (encoding a cysteine protease) (Mangold
et al., 2004). As for RNAIII of Staphylococcus aureus, Pel sRNA
displays bifunctionality, being an effector of virulence factor
expression and encoding a haemolysin. Lastly, RivX sRNA is
The role of two sRNAs, RsmY and RsmZ, in P. aeruginosa
is a nice example of the interconnection between the
regulation of metabolism and pathogenesis. In addition
to sequestering the transcriptional regulator RsmA (see
‘sRNA and cellular metabolism’ above) they also affect
the expression of a variety of genes important for virulence
and survival (Heurlier et al., 2004; Kay et al., 2006), such
as those implicated in pyocyanin, hydrogen cyanide and
PA-IL lectin synthesis. RsmA plays an important role in the
control of the switch between acute infection and chronic
infection through the regulation of a type 3 secretion
system and motility or a type 6 secretion system and
biofilm formation (Bordi et al., 2010; Mulcahy et al., 2008).
Of note, overexpression of RsmZ coincides with reduced
biofilm development that is particularly associated with the
pathogenicity of P. aeruginosa (Petrova & Sauer, 2010).
1014
sRNA in the pathogenesis of Chlamydia trachomatis
One last example is the involvement of the sRNA IhtA
in the virulence of Chlamydia trachomatis, an obligate
Downloaded from www.microbiologyresearch.org by
IP: 88.99.165.207
On: Mon, 31 Jul 2017 20:23:17
Microbiology 160
Roles of sRNAs
intracellular pathogen, and the leading cause of blindness
and sexually transmitted urogenital infections (Moulder,
1991). The chlamydial life cycle is controlled by two
histone-like proteins, Hc1 and Hc2, expressed only during
the late stages of the cycle. Their expression is concomitant
with the differentiation of reticulate bodies into elementary
bodies, the infectious but inactive form of the bacteria
(Grieshaber et al., 2006; Shaw et al., 2000). When Chlamydia
trachomatis undergoes differentiation from the elementary
body to the reticulate body, after bacterial entry into host
cells, the abundance of the sRNA IhtA increases and the level
of Hc1 decreases (Grieshaber et al., 2006). However, when
the reticulate body differentiates into the elementary body,
IhtA transcription decreases and Hc1 synthesis takes place.
Therefore, IhtA acts indirectly as a global transcriptional
activator avoiding chromatin condensation during the
replicative stage of Chlamydia trachomatis.
analysis of their physiological role in the cell, technically
laborious (i.e. construction of deletion strains or libraries of
sRNA-overexpressing plasmids), will constitute one of the
main challenges to increase our understanding of bacterial
behaviour and metabolism, especially during infection or
the stress responses.
Acknowledgements
C. M. was funded by a thesis grant awarded by the Ministère de
l’Enseignement Supérieur et de la Recherche, and was co-supervised
by N. V. and J. C. G. This study was supported by a grant from Agence
Nationale de la Recherche in the frame of the transnational ERA-NET
PathoGenoMics program (ANR-08-PATH-008-01).
References
Aiba, H. (2007). Mechanism of RNA silencing by Hfq-binding small
RNAs. Curr Opin Microbiol 10, 134–139.
Concluding remarks
Altuvia, S. (2007). Identification of bacterial small non-coding RNAs:
The transcriptional activity of the bacterial cell is mainly
directed through the production of ‘non-translatable’ RNA.
The huge amount of data obtained by next-generation
sequencing technologies as well as by progress in bioinformatics also reveals that the intergenic fraction of the
genome must be taken into consideration as it encodes
RNAs important in the fine regulation of cellular processes.
Sophisticated mechanisms such as riboswitches, proteinbinding sRNAs, trans-encoded base-pairing sRNAs and
some cis-encoding base-pairing sRNAs mediate responses
to changing environmental conditions by modulating metabolic pathways or stress responses. This highlights the
complexity of the regulatory network that exists in prokaryotic cells and we are likely to be only at the beginning of a
vast field of research involving RNA molecules. As suggested
by Beisel & Storz (2011), this type of regulation seems
favourable for the cells by reducing metabolic cost, bringing
additional levels of regulation or allowing faster regulation
because of the absence of the translation step. In addition,
post-transcriptional regulation by sRNA allows bacteria to
respond to signals in a rapid and sensitive manner.
In this review, we have pointed out the diversity of physiological processes in which sRNA molecules are key
actors: metabolism, QS, stress response and virulence.
This shows the central role of sRNAs to help bacteria cope
with environmental changes and to survive under stressful
conditions present in the host. During the infection process,
bacteria have to adapt rapidly to changing environmental
conditions and to escape the immune system. The numerous
examples presented in this review indicate that sRNAs are
required for a coordinated response and thus play a crucial
role in these processes. However, in comparison with the
high and still increasing number of sRNAs identified in
bacterial genomes, only a few of them have been hitherto
functionally characterized. The physiological relevance of
sRNA studies will be at the crossroads of computational,
transcriptomic and proteomic approaches. Nevertheless, an
http://mic.sgmjournals.org
experimental approaches. Curr Opin Microbiol 10, 257–261.
Altuvia, S., Weinstein-Fischer, D., Zhang, A., Postow, L. & Storz, G.
(1997). A small, stable RNA induced by oxidative stress: role as a
pleiotropic regulator and antimutator. Cell 90, 43–53.
Altuvia, S., Zhang, A., Argaman, L., Tiwari, A. & Storz, G. (1998). The
Escherichia coli OxyS regulatory RNA represses fhlA translation by
blocking ribosome binding. EMBO J 17, 6069–6075.
Andersen, J. & Delihas, N. (1990). micF RNA binds to the 59 end of
ompF mRNA and to a protein from Escherichia coli. Biochemistry 29,
9249–9256.
Awad, M. M., Ellemor, D. M., Bryant, A. E., Matsushita, O., Boyd, R. L.,
Stevens, D. L., Emmins, J. J. & Rood, J. I. (2000). Construction and
virulence testing of a collagenase mutant of Clostridium perfringens.
Microb Pathog 28, 107–117.
Babitzke, P. & Romeo, T. (2007). CsrB sRNA family: sequestration of
RNA-binding regulatory proteins. Curr Opin Microbiol 10, 156–163.
Bardill, J. P., Zhao, X. & Hammer, B. K. (2011). The Vibrio cholerae
quorum sensing response is mediated by Hfq-dependent sRNA/
mRNA base pairing interactions. Mol Microbiol 80, 1381–1394.
Barrangou, R. (2013). CRISPR–Cas systems and RNA-guided inter-
ference. Wiley Interdiscip Rev RNA 4, 267–278.
Bassler, B. L., Wright, M. & Silverman, M. R. (1994). Sequence and
function of LuxO, a negative regulator of luminescence in Vibrio
harveyi. Mol Microbiol 12, 403–412.
Beisel, C. L. & Storz, G. (2011). The base-pairing RNA spot 42
participates in a multioutput feedforward loop to help enact catabolite
repression in Escherichia coli. Mol Cell 41, 286–297.
Beisel, C. L., Updegrove, T. B., Janson, B. J. & Storz, G. (2012).
Multiple factors dictate target selection by Hfq-binding small RNAs.
EMBO J 31, 1961–1974.
Boisset, S., Geissmann, T., Huntzinger, E., Fechter, P., Bendridi, N.,
Possedko, M., Chevalier, C., Helfer, A. C., Benito, Y. & other authors
(2007). Staphylococcus aureus RNAIII coordinately represses the
synthesis of virulence factors and the transcription regulator Rot by
an antisense mechanism. Genes Dev 21, 1353–1366.
Bordi, C., Lamy, M.-C., Ventre, I., Termine, E., Hachani, A., Fillet, S.,
Roche, B., Bleves, S., Méjean, V. & other authors (2010). Regulatory
RNAs and the HptB/RetS signalling pathways fine-tune Pseudomonas
aeruginosa pathogenesis. Mol Microbiol 76, 1427–1443.
Downloaded from www.microbiologyresearch.org by
IP: 88.99.165.207
On: Mon, 31 Jul 2017 20:23:17
1015
C. Michaux and others
Bradley, E. S., Bodi, K., Ismail, A. M. & Camilli, A. (2011). A genome-
wide approach to discovery of small RNAs involved in regulation of
virulence in Vibrio cholerae. PLoS Pathog 7, e1002126.
Gottesman, S. (2005). Micros for microbes: non-coding regulatory
RNAs in bacteria. Trends Genet 21, 399–404.
Gottesman, S. & Storz, G. (2011). Bacterial small RNA regulators:
antisense RNAs. Curr Opin Microbiol 10, 102–109.
versatile roles and rapidly evolving variations. Cold Spring Harb
Perspect Biol 3, a003798.
Castanie-Cornet, M. P., Penfound, T. A., Smith, D., Elliott, J. F. &
Foster, J. W. (1999). Control of acid resistance in Escherichia coli.
Grieshaber, N. A., Grieshaber, S. S., Fischer, E. R. & Hackstadt, T.
(2006). A small RNA inhibits translation of the histone-like protein
J Bacteriol 181, 3525–3535.
Hc1 in Chlamydia trachomatis. Mol Microbiol 59, 541–550.
Cheung, A. L., Eberhardt, K. J., Chung, E., Yeaman, M. R., Sullam,
P. M., Ramos, M. & Bayer, A. S. (1994). Diminished virulence of a
Guillier, M., Gottesman, S. & Storz, G. (2006). Modulating the outer
membrane with small RNAs. Genes Dev 20, 2338–2348.
sar2/agr2 mutant of Staphylococcus aureus in the rabbit model of
endocarditis. J Clin Invest 94, 1815–1822.
Hammer, B. K. & Bassler, B. L. (2007). Regulatory small RNAs
Brantl, S. (2007). Regulatory mechanisms employed by cis-encoded
Constantinidou, C., Hobman, J. L., Griffiths, L., Patel, M. D., Penn,
C. W., Cole, J. A. & Overton, T. W. (2006). A reassessment of the FNR
regulon and transcriptomic analysis of the effects of nitrate, nitrite,
NarXL, and NarQP as Escherichia coli K12 adapts from aerobic to
anaerobic growth. J Biol Chem 281, 4802–4815.
Coyer, J., Andersen, J., Forst, S. A., Inouye, M. & Delihas, N. (1990).
micF RNA in ompB mutants of Escherichia coli: different pathways
regulate micF RNA levels in response to osmolarity and temperature
change. J Bacteriol 172, 4143–4150.
De Lay, N. & Gottesman, S. (2012). A complex network of small non-
coding RNAs regulate motility in Escherichia coli. Mol Microbiol 86,
524–538.
Deutscher, J., Francke, C. & Postma, P. W. (2006). How
phosphotransferase system-related protein phosphorylation regulates
carbohydrate metabolism in bacteria. Microbiol Mol Biol Rev 70, 939–
1031.
Durand, S. & Storz, G. (2010). Reprogramming of anaerobic
metabolism by the FnrS small RNA. Mol Microbiol 75, 1215–1231.
Ferrara, S., Brugnoli, M., De Bonis, A., Righetti, F., Delvillani, F.,
Dehò, G., Horner, D., Briani, F. & Bertoni, G. (2012). Comparative
profiling of Pseudomonas aeruginosa strains reveals differential
expression of novel unique and conserved small RNAs. PLoS ONE
7, e36553.
circumvent the conventional quorum sensing pathway in pandemic
Vibrio cholerae. Proc Natl Acad Sci U S A 104, 11145–11149.
Heidrich, N., Chinali, A., Gerth, U. & Brantl, S. (2006). The small
untranslated RNA SR1 from the Bacillus subtilis genome is involved in
the regulation of arginine catabolism. Mol Microbiol 62, 520–536.
Heidrich, N., Moll, I. & Brantl, S. (2007). In vitro analysis of the
interaction between the small RNA SR1 and its primary target ahrC
mRNA. Nucleic Acids Res 35, 4331–4346.
Heroven, A. K., Böhme, K. & Dersch, P. (2012). The Csr/Rsm system
of Yersinia and related pathogens: a post-transcriptional strategy for
managing virulence. RNA Biol 9, 379–391.
Hershberg, R., Altuvia, S. & Margalit, H. (2003). A survey of small
RNA-encoding genes in Escherichia coli. Nucleic Acids Res 31, 1813–
1820.
Herskovits, A. A., Bochkareva, E. S. & Bibi, E. (2000). New prospects
in studying the bacterial signal recognition particle pathway. Mol
Microbiol 38, 927–939.
Heurlier, K., Williams, F., Heeb, S., Dormond, C., Pessi, G., Singer,
D., Cámara, M., Williams, P. & Haas, D. (2004). Positive control of
swarming, rhamnolipid synthesis, and lipase production by the
posttranscriptional RsmA/RsmZ system in Pseudomonas aeruginosa
PAO1. J Bacteriol 186, 2936–2945.
Hobbs, E. C., Astarita, J. L. & Storz, G. (2010). Small RNAs and small
Microbiol 8, 623–633.
proteins involved in resistance to cell envelope stress and acid shock in
Escherichia coli: analysis of a bar-coded mutant collection. J Bacteriol
192, 59–67.
Fozo, E. M., Hemm, M. R. & Storz, G. (2008). Small toxic proteins and
Homola, A. D. & Dekker, E. E. (1967). Decarboxylation of c-
the antisense RNAs that repress them. Microbiol Mol Biol Rev 72, 579–
589.
hydroxyglutamate by glutamate decarboxylase of Escherichia coli
(ATCC 11246). Biochemistry 6, 2626–2634.
Freeman, J. A. & Bassler, B. L. (1999). A genetic analysis of the
Huntzinger, E., Boisset, S., Saveanu, C., Benito, Y., Geissmann, T.,
Namane, A., Lina, G., Etienne, J., Ehresmann, B. & other authors
(2005). Staphylococcus aureus RNAIII and the endoribonuclease III
Flemming, H.-C. & Wingender, J. (2010). The biofilm matrix. Nat Rev
function of LuxO, a two-component response regulator involved in
quorum sensing in Vibrio harveyi. Mol Microbiol 31, 665–677.
Gardan, R., Rapoport, G. & Débarbouillé, M. (1997). Role of the
coordinately regulate spa gene expression. EMBO J 24, 824–835.
transcriptional activator RocR in the arginine-degradation pathway of
Bacillus subtilis. Mol Microbiol 24, 825–837.
Jacques, J.-F., Jang, S., Prévost, K., Desnoyers, G., Desmarais, M.,
Imlay, J. & Massé, E. (2006). RyhB small RNA modulates the free
Georgellis, D., Kwon, O. & Lin, E. C. (2001). Quinones as the redox
intracellular iron pool and is essential for normal growth during iron
limitation in Escherichia coli. Mol Microbiol 62, 1181–1190.
signal for the Arc two-component system of bacteria. Science 292,
2314–2316.
Jin, Y., Watt, R. M., Danchin, A. & Huang, J. D. (2009). Small noncoding
Gillaspy, A. F., Hickmon, S. G., Skinner, R. A., Thomas, J. R., Nelson,
C. L. & Smeltzer, M. S. (1995). Role of the accessory gene regulator
RNA GcvB is a novel regulator of acid resistance in Escherichia coli.
BMC Genomics 10, 165.
(agr) in pathogenesis of staphylococcal osteomyelitis. Infect Immun
63, 3373–3380.
Johansson, J. & Cossart, P. (2003). RNA-mediated control of
Gong, H., Vu, G.-P., Bai, Y., Chan, E., Wu, R., Yang, E., Liu, F. & Lu, S.
(2011). A Salmonella small non-coding RNA facilitates bacterial
invasion and intracellular replication by modulating the expression of
virulence factors. PLoS Pathog 7, e1002120.
González, N., Heeb, S., Valverde, C., Kay, E., Reimmann, C., Junier, T.
& Haas, D. (2008). Genome-wide search reveals a novel GacA-
regulated small RNA in Pseudomonas species. BMC Genomics 9,
167.
1016
virulence gene expression in bacterial pathogens. Trends Microbiol 11,
280–285.
Johnson, J. R., Clabots, C. & Rosen, H. (2006). Effect of inactivation
of the global oxidative stress regulator oxyR on the colonization
ability of Escherichia coli O1 : K1 : H7 in a mouse model of ascending
urinary tract infection. Infect Immun 74, 461–468.
Jørgensen, M. G., Thomason, M. K., Havelund, J., Valentin-Hansen,
P. & Storz, G. (2013). Dual function of the McaS small RNA in
controlling biofilm formation. Genes Dev 27, 1132–1145.
Downloaded from www.microbiologyresearch.org by
IP: 88.99.165.207
On: Mon, 31 Jul 2017 20:23:17
Microbiology 160
Roles of sRNAs
Kang, Y., Weber, K. D., Qiu, Y., Kiley, P. J. & Blattner, F. R. (2005).
Mandin, P. & Gottesman, S. (2010). Integrating anaerobic/aerobic
Genome-wide expression analysis indicates that FNR of Escherichia
coli K-12 regulates a large number of genes of unknown function.
J Bacteriol 187, 1135–1160.
sensing and the general stress response through the ArcZ small RNA.
EMBO J 29, 3094–3107.
Kay, E., Humair, B., Dénervaud, V., Riedel, K., Spahr, S., Eberl, L.,
Valverde, C. & Haas, D. (2006). Two GacA-dependent small RNAs
modulate the quorum-sensing response in Pseudomonas aeruginosa.
J Bacteriol 188, 6026–6033.
Kim, Y.-M., Ogawa, W., Tamai, E., Kuroda, T., Mizushima, T. &
Tsuchiya, T. (2002). Purification, reconstitution, and characterization
+
of Na /serine symporter, SstT, of Escherichia coli. J Biochem 132,
71–76.
Kint, G., De Coster, D., Marchal, K., Vanderleyden, J. & De
Keersmaecker, S. C. J. (2010). The small regulatory RNA molecule
MicA is involved in Salmonella enterica serovar Typhimurium biofilm
formation. BMC Microbiol 10, 276.
Klenk, M., Koczan, D., Guthke, R., Nakata, M., Thiesen, H.-J.,
Podbielski, A. & Kreikemeyer, B. (2005). Global epithelial cell
transcriptional responses reveal Streptococcus pyogenes Fas regulator
activity association with bacterial aggressiveness. Cell Microbiol 7,
1237–1250.
Koo, J. T., Alleyne, T. M., Schiano, C. A., Jafari, N. & Lathem, W. W.
(2011). Global discovery of small RNAs in Yersinia pseudotuberculosis
identifies Yersinia-specific small, noncoding RNAs required for
virulence. Proc Natl Acad Sci U S A 108, E709–E717.
Korem, M., Gov, Y., Kiran, M. D. & Balaban, N. (2005). Transcriptional
profiling of target of RNAIII-activating protein, a master regulator of
staphylococcal virulence. Infect Immun 73, 6220–6228.
Kreikemeyer, B., Boyle, M. D., Buttaro, B. A., Heinemann, M. &
Podbielski, A. (2001). Group A streptococcal growth phase-associated
virulence factor regulation by a novel operon (Fas) with homologies
to two-component-type regulators requires a small RNA molecule.
Mol Microbiol 39, 392–406.
Lai, L. B., Vioque, A., Kirsebom, L. A. & Gopalan, V. (2010). Unexpected
diversity of RNase P, an ancient tRNA processing enzyme: challenges
and prospects. FEBS Lett 584, 287–296.
Lapouge, K., Schubert, M., Allain, F. H.-T. & Haas, D. (2008).
Mangold, M., Siller, M., Roppenser, B., Vlaminckx, B. J. M., Penfound,
T. A., Klein, R., Novak, R., Novick, R. P. & Charpentier, E. (2004).
Synthesis of group A streptococcal virulence factors is controlled by a
regulatory RNA molecule. Mol Microbiol 53, 1515–1527.
Massé, E. & Gottesman, S. (2002). A small RNA regulates the
expression of genes involved in iron metabolism in Escherichia coli.
Proc Natl Acad Sci U S A 99, 4620–4625.
Massé, E., Escorcia, F. E. & Gottesman, S. (2003). Coupled degradation
of a small regulatory RNA and its mRNA targets in Escherichia coli.
Genes Dev 17, 2374–2383.
Massé, E., Salvail, H., Desnoyers, G. & Arguin, M. (2007). Small
RNAs controlling iron metabolism. Curr Opin Microbiol 10, 140–145.
Mey, A. R., Craig, S. A. & Payne, S. M. (2005). Characterization of
Vibrio cholerae RyhB: the RyhB regulon and role of ryhB in biofilm
formation. Infect Immun 73, 5706–5719.
Mika, F. & Hengge, R. (2013). Small regulatory RNAs in the control of
motility and biofilm formation in E. coli and Salmonella. Int J Mol Sci
14, 4560–4579.
Miller, M. B., Skorupski, K., Lenz, D. H., Taylor, R. K. & Bassler,
B. L. (2002). Parallel quorum sensing systems converge to regulate
virulence in Vibrio cholerae. Cell 110, 303–314.
Modi, S. R., Camacho, D. M., Kohanski, M. A., Walker, G. C. & Collins,
J. J. (2011). Functional characterization of bacterial sRNAs using a
network biology approach. Proc Natl Acad Sci U S A 108, 15522–
15527.
Monteiro, C., Papenfort, K., Hentrich, K., Ahmad, I., Le Guyon, S.,
Reimann, R., Grantcharova, N. & Römling, U. (2012). Hfq and
Hfq-dependent small RNAs are major contributors to multicellular
development in Salmonella enterica serovar Typhimurium. RNA Biol
9, 489–502.
Moore, S. D. & Sauer, R. T. (2007). The tmRNA system for trans-
lational surveillance and ribosome rescue. Annu Rev Biochem 76, 101–
124.
Gac/Rsm signal transduction pathway of gamma-proteobacteria: from
RNA recognition to regulation of social behaviour. Mol Microbiol 67,
241–253.
Morfeldt, E., Taylor, D., von Gabain, A. & Arvidson, S. (1995).
Leday, T. V., Gold, K. M., Kinkel, T. L., Roberts, S. A., Scott, J. R. &
McIver, K. S. (2008). TrxR, a new CovR-repressed response regulator
Morita, T., Kawamoto, H., Mizota, T., Inada, T. & Aiba, H. (2004).
Activation of alpha-toxin translation in Staphylococcus aureus by the
trans-encoded antisense RNA, RNAIII. EMBO J 14, 4569–4577.
that activates the Mga virulence regulon in group A Streptococcus.
Infect Immun 76, 4659–4668.
Enolase in the RNA degradosome plays a crucial role in the rapid
decay of glucose transporter mRNA in the response to phosphosugar
stress in Escherichia coli. Mol Microbiol 54, 1063–1075.
Lenz, D. H., Mok, K. C., Lilley, B. N., Kulkarni, R. V., Wingreen, N. S. &
Bassler, B. L. (2004). The small RNA chaperone Hfq and multiple
Morita, T., Mochizuki, Y. & Aiba, H. (2006). Translational repression
small RNAs control quorum sensing in Vibrio harveyi and Vibrio
cholerae. Cell 118, 69–82.
is sufficient for gene silencing by bacterial small noncoding RNAs
in the absence of mRNA destruction. Proc Natl Acad Sci U S A 103,
4858–4863.
Lilley, B. N. & Bassler, B. L. (2000). Regulation of quorum sensing in
Moulder, J. W. (1991). Interaction of chlamydiae and host cells in
Vibrio harveyi by LuxO and sigma-54. Mol Microbiol 36, 940–954.
vitro. Microbiol Rev 55, 143–190.
Lyon, G. J. & Novick, R. P. (2004). Peptide signaling in Staphylococcus
Mraheil, M. A., Billion, A., Kuenne, C., Pischimarov, J., Kreikemeyer,
B., Engelmann, S., Hartke, A., Giard, J.-C., Rupnik, M. & other
authors (2010). Comparative genome-wide analysis of small RNAs of
aureus and other Gram-positive bacteria. Peptides 25, 1389–1403.
Lyristis, M., Bryant, A. E., Sloan, J., Awad, M. M., Nisbet, I. T., Stevens,
D. L. & Rood, J. I. (1994). Identification and molecular analysis of
a locus that regulates extracellular toxin production in Clostridium
perfringens. Mol Microbiol 12, 761–777.
Madhugiri, R., Basineni, S. R. & Klug, G. (2010). Turn-over of the
small non-coding RNA RprA in E. coli is influenced by osmolarity.
Mol Genet Genomics 284, 307–318.
major Gram-positive pathogens: from identification to application.
Microb Biotechnol 3, 658–676.
Mraheil, M. A., Billion, A., Mohamed, W., Mukherjee, K., Kuenne, C.,
Pischimarov, J., Krawitz, C., Retey, J., Hartsch, T. & other authors
(2011). The intracellular sRNA transcriptome of Listeria monocyto-
Majdalani, N., Hernandez, D. & Gottesman, S. (2002). Regulation
genes during growth in macrophages. Nucleic Acids Res 39, 4235–
4248.
and mode of action of the second small RNA activator of RpoS
translation, RprA. Mol Microbiol 46, 813–826.
Mulcahy, H., O’Callaghan, J., O’Grady, E. P., Maciá, M. D., Borrell, N.,
Gómez, C., Casey, P. G., Hill, C., Adams, C. & other authors (2008).
http://mic.sgmjournals.org
Downloaded from www.microbiologyresearch.org by
IP: 88.99.165.207
On: Mon, 31 Jul 2017 20:23:17
1017
C. Michaux and others
Pseudomonas aeruginosa RsmA plays an important role during
murine infection by influencing colonization, virulence, persistence,
and pulmonary inflammation. Infect Immun 76, 632–638.
Rice, J. B. & Vanderpool, C. K. (2011). The small RNA SgrS controls
Novick, R. P. (2003). Autoinduction and signal transduction in the
Richards, G. R. & Vanderpool, C. K. (2011). Molecular call and
regulation of staphylococcal virulence. Mol Microbiol 48, 1429–1449.
Novick, R. P. & Geisinger, E. (2008). Quorum sensing in staphylococci.
response: the physiology of bacterial small RNAs. Biochim Biophys
Acta 1809, 525–531.
Annu Rev Genet 42, 541–564.
Richter, C., Chang, J. T. & Fineran, P. C. (2012). Function and
Novick, R. P. & Muir, T. W. (1999). Virulence gene regulation by
regulation of clustered regularly interspaced short palindromic repeats
(CRISPR)/CRISPR associated (Cas) systems. Viruses 4, 2291–2311.
sugar-phosphate accumulation by regulating multiple PTS genes.
Nucleic Acids Res 39, 3806–3819.
peptides in staphylococci and other Gram-positive bacteria. Curr Opin
Microbiol 2, 40–45.
Roberts, S. A. & Scott, J. R. (2007). RivR and the small RNA RivX: the
Novick, R. P., Ross, H. F., Projan, S. J., Kornblum, J., Kreiswirth, B. &
Moghazeh, S. (1993). Synthesis of staphylococcal virulence factors is
missing links between the CovR regulatory cascade and the Mga
regulon. Mol Microbiol 66, 1506–1522.
controlled by a regulatory RNA molecule. EMBO J 12, 3967–3975.
Romeo, T., Gong, M., Liu, M. Y. & Brun-Zinkernagel, A. M. (1993).
Obana, N., Nomura, N. & Nakamura, K. (2013). Structural requirement
Identification and molecular characterization of csrA, a pleiotropic
gene from Escherichia coli that affects glycogen biosynthesis, gluconeogenesis, cell size, and surface properties. J Bacteriol 175, 4744–4755.
in Clostridium perfringens collagenase mRNA 59 leader sequence
for translational induction through small RNA-mRNA base pairing.
J Bacteriol 195, 2937–2946.
Ogawa, W., Kim, Y. M., Mizushima, T. & Tsuchiya, T. (1998). Cloning
and expression of the gene for the Na+-coupled serine transporter
from Escherichia coli and characteristics of the transporter. J Bacteriol
180, 6749–6752.
Ohtani, K., Kawsar, H. I., Okumura, K., Hayashi, H. & Shimizu, T.
(2003). The VirR/VirS regulatory cascade affects transcription of
plasmid-encoded putative virulence genes in Clostridium perfringens
strain 13. FEMS Microbiol Lett 222, 137–141.
Opdyke, J. A., Kang, J.-G. & Storz, G. (2004). GadY, a small-RNA
regulator of acid response genes in Escherichia coli. J Bacteriol 186,
6698–6705.
Opdyke, J. A., Fozo, E. M., Hemm, M. R. & Storz, G. (2011). RNase III
participates in GadY-dependent cleavage of the gadX–gadW mRNA.
J Mol Biol 406, 29–43.
Papenfort, K., Pfeiffer, V., Mika, F., Lucchini, S., Hinton, J. C. D. &
Vogel, J. (2006). SE-dependent small RNAs of Salmonella respond to
Romeo, T., Vakulskas, C. A. & Babitzke, P. (2013). Post-transcrip-
tional regulation on a global scale: form and function of Csr/Rsm
systems. Environ Microbiol 15, 313–324.
Rutherford, S. T., van Kessel, J. C., Shao, Y. & Bassler, B. L. (2011).
AphA and LuxR/HapR reciprocally control quorum sensing in vibrios.
Genes Dev 25, 397–408.
Salmon, K., Hung, S. P., Mekjian, K., Baldi, P., Hatfield, G. W. &
Gunsalus, R. P. (2003). Global gene expression profiling in Escherichia
coli K12. The effects of oxygen availability and FNR. J Biol Chem 278,
29837–29855.
Salvail, H., Lanthier-Bourbonnais, P., Sobota, J. M., Caza, M.,
Benjamin, J.-A. M., Mendieta, M. E. S., Lépine, F., Dozois, C. M.,
Imlay, J. & Massé, E. (2010). A small RNA promotes siderophore
production through transcriptional and metabolic remodeling. Proc
Natl Acad Sci U S A 107, 15223–15228.
Sharma, C. M. & Vogel, J. (2009). Experimental approaches for the
discovery and characterization of regulatory small RNA. Curr Opin
Microbiol 12, 536–546.
membrane stress by accelerating global omp mRNA decay. Mol
Microbiol 62, 1674–1688.
Sharma, C. M., Darfeuille, F., Plantinga, T. H. & Vogel, J. (2007). A
Papenfort, K., Sun, Y., Miyakoshi, M., Vanderpool, C. K. & Vogel, J.
(2013). Small RNA-mediated activation of sugar phosphatase mRNA
small RNA regulates multiple ABC transporter mRNAs by targeting
C/A-rich elements inside and upstream of ribosome-binding sites.
Genes Dev 21, 2804–2817.
regulates glucose homeostasis. Cell 153, 426–437.
Pellin, D., Miotto, P., Ambrosi, A., Cirillo, D. M. & Di Serio, C. (2012).
A genome-wide identification analysis of small regulatory RNAs in
Mycobacterium tuberculosis by RNA-Seq and conservation analysis.
PLoS ONE 7, e32723.
Petrova, O. E. & Sauer, K. (2010). The novel two-component
regulatory system BfiSR regulates biofilm development by controlling
the small RNA rsmZ through CafA. J Bacteriol 192, 5275–5288.
Pichon, C. & Felden, B. (2008). Small RNA gene identification and
mRNA target predictions in bacteria. Bioinformatics 24, 2807–2813.
Podkaminski, D. & Vogel, J. (2010). Small RNAs promote mRNA
Sharma, C. M., Papenfort, K., Pernitzsch, S. R., Mollenkopf, H.-J.,
Hinton, J. C. D. & Vogel, J. (2011). Pervasive post-transcriptional
control of genes involved in amino acid metabolism by the Hfqdependent GcvB small RNA. Mol Microbiol 81, 1144–1165.
Shaw, E. I., Dooley, C. A., Fischer, E. R., Scidmore, M. A., Fields, K. A.
& Hackstadt, T. (2000). Three temporal classes of gene expression
during the Chlamydia trachomatis developmental cycle. Mol Microbiol
37, 913–925.
Shenkman, B., Varon, D., Tamarin, I., Dardik, R., Peisachov, M.,
Savion, N. & Rubinstein, E. (2002). Role of agr (RNAIII) in Sta-
stability to activate the synthesis of virulence factors. Mol Microbiol
78, 1327–1331.
phylococcus aureus adherence to fibrinogen, fibronectin, platelets and
endothelial cells under static and flow conditions. J Med Microbiol 51,
747–754.
Pulvermacher, S. C., Stauffer, L. T. & Stauffer, G. V. (2009). The
Shimizu, T., Yaguchi, H., Ohtani, K., Banu, S. & Hayashi, H. (2002).
small RNA GcvB regulates sstT mRNA expression in Escherichia coli.
J Bacteriol 191, 238–248.
Clostridial VirR/VirS regulon involves a regulatory RNA molecule for
expression of toxins. Mol Microbiol 43, 257–265.
Ramani, N., Hedeshian, M. & Freundlich, M. (1994). micF antisense
Shioya, K., Michaux, C., Kuenne, C., Hain, T., Verneuil, N.,
Budin-Verneuil, A., Hartsch, T., Hartke, A. & Giard, J.-C. (2011).
RNA has a major role in osmoregulation of OmpF in Escherichia coli.
J Bacteriol 176, 5005–5010.
Revelles, O., Millard, P., Nougayrède, J.-P., Dobrindt, U., Oswald, E.,
Létisse, F. & Portais, J.-C. (2013). The carbon storage regulator (Csr)
system exerts a nutrient-specific control over central metabolism
in Escherichia coli strain Nissle 1917. PLoS ONE 8, e66386.
1018
Genome-wide identification of small RNAs in the opportunistic
pathogen Enterococcus faecalis V583. PLoS ONE 6, e23948.
Silvaggi, J. M., Perkins, J. B. & Losick, R. (2006). Genes for small,
noncoding RNAs under sporulation control in Bacillus subtilis.
J Bacteriol 188, 532–541.
Downloaded from www.microbiologyresearch.org by
IP: 88.99.165.207
On: Mon, 31 Jul 2017 20:23:17
Microbiology 160
Roles of sRNAs
Sorek, R., Kunin, V. & Hugenholtz, P. (2008). CRISPR – a widespread
system that provides acquired resistance against phages in bacteria
and archaea. Nat Rev Microbiol 6, 181–186.
Sorger-Domenigg, T., Sonnleitner, E., Kaberdin, V. R. & Bläsi, U.
(2007). Distinct and overlapping binding sites of Pseudomonas
aeruginosa Hfq and RsmA proteins on the non-coding RNA RsmY.
Biochem Biophys Res Commun 352, 769–773.
Steuten, B., Schneider, S. & Wagner, R. (2014). 6S RNA: recent
answers – future questions. Mol Microbiol 91, 641–648.
Storz, G., Vogel, J. & Wassarman, K. M. (2011). Regulation by small
RNAs in bacteria: expanding frontiers. Mol Cell 43, 880–891.
Svenningsen, S. L., Tu, K. C. & Bassler, B. L. (2009). Gene dosage
compensation calibrates four regulatory RNAs to control Vibrio
cholerae quorum sensing. EMBO J 28, 429–439.
Thomason, M. K., Fontaine, F., De Lay, N. & Storz, G. (2012). A small
Vogel, J. (2009). A rough guide to the non-coding RNA world of
Salmonella. Mol Microbiol 71, 1–11.
Vogel, J. & Sharma, C. M. (2005). How to find small non-coding
RNAs in bacteria. Biol Chem 386, 1219–1238.
Vogel, J. & Wagner, E. G. H. (2007). Target identification of
small noncoding RNAs in bacteria. Curr Opin Microbiol 10, 262–
270.
Wassarman, K. M. (2007). 6S RNA: a small RNA regulator of
transcription. Curr Opin Microbiol 10, 164–168.
Wassarman, K. M., Repoila, F., Rosenow, C., Storz, G. & Gottesman,
S. (2001). Identification of novel small RNAs using comparative
genomics and microarrays. Genes Dev 15, 1637–1651.
Waters, C. M. & Bassler, B. L. (2005). Quorum sensing: cell-to-cell
communication in bacteria. Annu Rev Cell Dev Biol 21, 319–346.
RNA that regulates motility and biofilm formation in response to
changes in nutrient availability in Escherichia coli. Mol Microbiol 84,
17–35.
Waters, L. S. & Storz, G. (2009). Regulatory RNAs in bacteria. Cell
Toledo-Arana, A., Repoila, F. & Cossart, P. (2007). Small noncoding
Enterococcus faecalis plasmid pAD1 and its chromosomal homologs.
RNA Biol 9, 1498–1503.
RNAs controlling pathogenesis. Curr Opin Microbiol 10, 182–188.
Tramonti, A., Visca, P., De Canio, M., Falconi, M. & De Biase, D. (2002).
Functional characterization and regulation of gadX, a gene encoding an
AraC/XylS-like transcriptional activator of the Escherichia coli glutamic
acid decarboxylase system. J Bacteriol 184, 2603–2613.
Trotochaud, A. E. & Wassarman, K. M. (2006). 6S RNA regulation of
136, 615–628.
Weaver, K. E. (2012). The par toxin–antitoxin system from
Wilderman, P. J., Sowa, N. A., FitzGerald, D. J., FitzGerald, P. C.,
Gottesman, S., Ochsner, U. A. & Vasil, M. L. (2004). Identification of
tandem duplicate regulatory small RNAs in Pseudomonas aeruginosa
involved in iron homeostasis. Proc Natl Acad Sci U S A 101, 9792–
9797.
pspF transcription leads to altered cell survival at high pH. J Bacteriol
188, 3936–3943.
Winkler, W. C. & Breaker, R. R. (2005). Regulation of bacterial gene
Urbanowski, M. L., Stauffer, L. T. & Stauffer, G. V. (2000). The gcvB
Zhang, A., Altuvia, S., Tiwari, A., Argaman, L., Hengge-Aronis, R. &
Storz, G. (1998). The OxyS regulatory RNA represses rpoS translation
gene encodes a small untranslated RNA involved in expression of the
dipeptide and oligopeptide transport systems in Escherichia coli. Mol
Microbiol 37, 856–868.
Vanderpool, C. K. & Gottesman, S. (2004). Involvement of a
novel transcriptional activator and small RNA in post-transcriptional
regulation of the glucose phosphoenolpyruvate phosphotransferase
system. Mol Microbiol 54, 1076–1089.
expression by riboswitches. Annu Rev Microbiol 59, 487–517.
and binds the Hfq (HF-I) protein. EMBO J 17, 6061–6068.
Zhang, A., Wassarman, K. M., Rosenow, C., Tjaden, B. C., Storz, G. &
Gottesman, S. (2003). Global analysis of small RNA and mRNA
targets of Hfq. Mol Microbiol 50, 1111–1124.
Zhang, Y., Zhang, Z., Ling, L., Shi, B. & Chen, R. (2004). Conservation
Vecerek, B., Moll, I. & Bläsi, U. (2007). Control of Fur synthesis by the
analysis of small RNA genes in Escherichia coli. Bioinformatics 20, 599–
603.
non-coding RNA RyhB and iron-responsive decoding. EMBO J 26,
965–975.
Edited by: S. Spiro
http://mic.sgmjournals.org
Downloaded from www.microbiologyresearch.org by
IP: 88.99.165.207
On: Mon, 31 Jul 2017 20:23:17
1019