SNORNAS HOMOLOGY SEARCH

Transcription

1 S HOMOLOGY SEARCH Stephanie Kehr Bioinformatics University of Leipzig Herbstseminar, 2009

2 MOTIVATION one of most abundand group of ncrna in eucaryotic cells suprisingly diverse regulating functions

3 SNORNAS - STRUCTURE AND FUNCTION CD-box guide 2 -O-methylation(s) HACA-box guide pseudouridylation(s)

4 SNORNPS - PROTEINS 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

5 SNORNPS - PROTEINS CD-snoRNP -> protein bridge to secure enzym catalytic component fibrillarin ->2 -O-methyltransferase Nop56/58 binds enzym kink-turn formed by L7Ae NHPX

6 SNORNAS - DIFFERENT GENOMIC ORGANISATION mostly intron encoded in vertebrata mostly independent with promotors in yeast

7 SNORNAS - DIFFERENT GENOMIC ORGANISATION snornas often clustered in hostgenes hotspot in vertebrata: gas-5 like hostgene

8 SNORNAS & 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

9 SNORNAS & 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

10 BRAIN SPECIFIC SNORNAS 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

11 SNORNAS & RNA SILENCING PATHWAY sdrnas microrna precursors high abundand sdrnas are derived from weakly expressed snornas orphan snornas

12 SNORNAS &... trna modification in archae telomerase RNA ribonuclease MRP RNA

13 SNORNPS - MATURATION & TRAFFICKING 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

14 EVOLUTION GENERAL 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

15 EVOLUTION HOMOLOGY - APPROACHES 1.sequence & structure homology conservation of sequence and structure recognisable by BLAST, INFERNAL, GotohScan, 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

16 EVOLUTION HOMOLOGY - OBSERVATIONS 1. recombination of guiding function two modifications guided by different snornas in one organism have a single guide snorna in another organism

17 EVOLUTION 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

18 LITERATURE LITERATURE I J. P. Bachellerie, J. Cavaillé, and A. Hüttenhofer. The expanding snorna world. Biochimie, 84(8):775 90, Aug G. Dieci, M. Preti, and B. Montanini. Eukaryotic snornas: a paradigm for gene expression flexibility. Genomics, 94(2):83 8, Aug 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.

19 LITERATURE LITERATURE 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): , Aug 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, R. J. Taft, E. A. Glazov, T. Lassmann, Y. Hayashizaki, P. Carninci, and J. S. Mattick. Small rnas derived from snornas. RNA, 15(7): , Jul 2009.

20 LITERATURE THANK YOU Sebastian, Hakim, Jana, Peter