SNO RNA S HOMOLOGY SEARCH
Stephanie Kehr
Bioinformatics
University of Leipzig
Herbstseminar, 2009
SNO RNA
M OTIVATION
one of most abundand group of ncRNA in eucaryotic cells
suprisingly diverse regulating functions
SNO RNA
SNO RNA S
- S TRUCTURE AND FUNCTION
CD-box guide 2’-O-methylation(s)
HACA-box guide pseudouridylation(s)
SNO RNA
SNO RNP S
- P ROTEINS
HACA-snoRNP -> direct
binding of enzym
catalytic component
Cbf5|diskerin
->pseudouridyl-synthase
kink-turn formed by
L7Ae|NHP2
binding of target
Gar1 -> binding/release of
target RNA
coordinative function
Nop10 ->associated with
other proteins
SNO RNA
SNO RNP S
- P ROTEINS
CD-snoRNP -> protein bridge
to secure enzym
catalytic component
fibrillarin
->2’-O-methyltransferase
Nop56/58 binds enzym
kink-turn formed by
L7Ae|NHPX
SNO RNA
SNO RNA S
- DIFFERENT GENOMIC ORGANISATION
mostly intron encoded in vertebrata
mostly independent with promotors in yeast
SNO RNA
SNO RNA S
- DIFFERENT GENOMIC ORGANISATION
snoRNAs often clustered in hostgenes
hotspot in vertebrata: gas-5 like hostgene
SNO RNA
SNO RNA S
& RIBOSOMES
snoRNAs located in nucleolus
most function in rRNA processing
known methylated nucleotides and pseudouridines located in key
regions of rRNA
are essential for fine-tuning of ribosome-function
endonucleotic cleavage of pre-rRNA
box-motifs responsible for targeting snoRNA to nucleolus
SNO RNA
SNO RNA S
& SPLICING
scaRNAs
share structure, box-motifs and guiding-function with ’normal’
snoRNAs
hybrids with HACA and CD domain or ’twins’
RNPs have same core proteins
targets on snRNAs
located at Cajal bodies
HACA domains share CAB-box-motif in apical loop
SNO RNA
BRAIN SPECIFIC SNO RNA S
tissue-specific expression
mostly CD-box snoRNAs
target mRNA of seretonin receptor
subject to genomic imprinting
maternal or paternal expressed
exception HBI-36 but this is encoded in seretonin receptor coding
region on X-chromosome
organized in tandem repeats
conserved 5’-GGACC...GGTCC-3’ terminal stem
SNO RNA
SNO RNA S
& RNA SILENCING PATHWAY
sdRNAs
microRNA precursors
high abundand sdRNAs are derived from weakly expressed
snoRNAs
’orphan’ snoRNAs
SNO RNA
SNO RNA S
& ...
tRNA modification in archae
telomerase RNA
ribonuclease MRP RNA
SNO RNA
SNO RNP S
- M ATURATION & T RAFFICKING
maturation takes place at Cajal Bodies
exact steps and involved proteins are not exactly known yet
known assembly factors
Naf1 <-> Gar1 (HACA)
Bcd1 <-> Nop56 (CD)
IBP160 in most cases about 40nts upstream of snoRNA
forwarding of mature snoRNPs to modification sites needed
-> probably these diverse regulating RNAs are regulated themself
through various mechanisms at several levels
E VOLUTION
G ENERAL
present in archae and eucaryotes -> emerged 2-3 billion years ago
high vertical, very low horizontal conservation
extensive variations in nucleotide but conserved box-motifs,
antisense-elements and structure
but also high similarity in nucleotides but different or no guiding
function
E VOLUTION
HOMOLOGY
- APPROACHES
1.sequence & structure homology
conservation of sequence and structure
recognisable by BLAST, INFERNAL, GotohScan ,...
2. functional homology
same guiding function
target prediction with RNAsnoop for H/ACAs
and RNAduplex for CDs
3.snoRNA clusters in orthologue hostgenes to find homologue
snoRNAs
E VOLUTION
HOMOLOGY
- OBSERVATIONS
1. recombination of guiding function
two modifications guided by different snoRNAs in one organism
have a single guide snoRNA in another organism
E VOLUTION
HOMOLOGY
- OBSERVATIONS
2. separation of guiding function
two modifications guides by one snoRNA in one organism are
guided by two differnt guide snoRNAs in another organism
L ITERATURE
L ITERATURE I
J. P. Bachellerie, J. Cavaillé, and A. Hüttenhofer.
The expanding snorna world.
Biochimie, 84(8):775–90, Aug 2002.
G. Dieci, M. Preti, and B. Montanini.
Eukaryotic snornas: a paradigm for gene expression flexibility.
Genomics, 94(2):83–8, Aug 2009.
A. G. Matera, R. M. Terns, and M. P. Terns.
Non-coding rnas: lessons from the small nuclear and small
nucleolar rnas.
Nat Rev Mol Cell Biol, 8(3):209–20, Mar 2007.
L ITERATURE
L ITERATURE II
P. Richard, X. Darzacq, E. Bertrand, B. E. Jády, C. Verheggen, and
T. Kiss.
A common sequence motif determines the cajal body-specific
localization of box h/aca scarnas.
EMBO J, 22(16):4283–93, Aug 2003.
P. Shao, J. H. Yang, H. Zhou, D. G. Guan, and L. H. Qu.
Genome-wide analysis of chicken snornas provides unique
implications for the evolution of vertebrate snornas.
BMC Genomics, 10:86, 2009.
R. J. Taft, E. A. Glazov, T. Lassmann, Y. Hayashizaki, P. Carninci,
and J. S. Mattick.
Small rnas derived from snornas.
RNA, 15(7):1233–40, Jul 2009.
L ITERATURE
T HANK YOU
Sebastian, Hakim, Jana, Peter