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Microrna Innovations and the Origin of Novel Cell Types

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Microrna Innovations and the Origin of Novel Cell Types MicroRNA innovations and the origin of novel cell types A. Tanzer1,2,3, P.F. Stadler1,2,4, G.P.Wagner3 1Bioinformatics Group, Department of Compute Science, University of Leipzig, Germany 2Institute for Theoretical Chemistry, University of Vienna, Austria [email protected] 3Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06511, USA 4The Santa Fe Institute, Santa Fe, USA Bled, Feb 20, 2009 Regulatory RNAs in an Eukaryote Cell pre−miRNA translational inhibition Protein vRNP Drosha RNAi RISC Ribosome pri−miRNA tRNA vRNA + vault proteins CAJAL BODY rRNA Introns NUCLEOLUS mRNA mRNA rRNA miRNA NUCLEUS Splicosome snoRNA Dicer pre−rRNA miRNA RNAse_MRP pre−mRNA snRNA scaRNA pre−miRNA Y_RNA + Ro Proteins 7SL_RNA + ? 7SL_RNA Y_RNA pre−tRNA RNAse_P vRNA Y RNP SRP tRNA Regulatory RNAs in an Eukaryote Cell pre−miRNA translational inhibition Protein vRNP Drosha RNAi RISC Ribosome pri−miRNA tRNA vRNA + vault proteins CAJAL BODY rRNA Introns NUCLEOLUS mRNA mRNA rRNA miRNA NUCLEUS Splicosome snoRNA Dicer pre−rRNA miRNA RNAse_MRPpre−mRNA snRNA scaRNA pre−miRNA Y_RNA + Ro Proteins 7SL_RNA + ? 7SL_RNA Y_RNA pre−tRNA RNAse_P vRNA Y RNP SRP tRNA What are MicroRNAs? ◮ small non-coding RNAs (ncRNAs) ◮ regulate gene expression ◮ target DNA and mRNA ◮ part of protein complexes Maturation of miRNAs A G U A A U U U A G U A U G A U G C U A A U U U U A ◮ G C C G miR-92-2 G A U primary-precursor micro RNA C miR-106a G U U U U _ U U U G A C U G U _ A U C G U U _ A U A _ A C G _ C C C _ U G G _ A C C G _ G U A G _ G G A U A UG G _ U U _ U A C G C _ U G G G _ C A U A C G U U G A G C U A C C A C A G C A C G G C U C G A C _ U C A U A C C A C G G C C U (pri-miRNA) G G A A U A G U U G U C U C U A C A G C G A _ _ A U G U A _ _ C U C A C U _G A C G U C A _ C C U U A A G GC U A _ U U AUAA A C U A U A G _ A AC A U U C G _ U A G U G U U A G U C A A A A C G U C U A A A C G U G U C G G U A U A U A A U U U U A U _ C G A C U U A C A A U U A G U U U U G C A G A U U U G C AGUUC A G CGU A U A U A G A G G U G A C C C U G U A C U A G U A G G G U U A U U U U A U G U U C A G A U U C G G A C C U CCU C A G U U U A A U U A CA A C U G U G A G C A C C U G G A U C G A A A U A A A A U A G C U A A U A C A U U U G G U A G U U A miR-18 C U A U A C A ◮ U G U G U C U A C A U A U A A U U G G A C miR-19b-2 C G G A C A U U A U U A C G U C G C C A U G G A U C C C U CU G C Cleavage I: Drosha G U G A C A U G C U G C U A A G C G A A C U G C C A A U A A U A C U U C U G AGA U A A U G A A G G A A C A A A A C A G U U U A U U C U C G U C A UG U ◮ A A U A _ A G A G UC G UA A C precursor miRNA (pre-miRNAs) G A A A U C G G U C G A C _ U A _ U U C A U _ A G C _ G U U U A C G G U A A U U U _ A C G A A C C C A C C A C C U A U G A U G A U U C ◮ G A U G U G G U C U G G G C A U C export to cytoplasm (exportin-5) G C G A A U U U A G C G C U U G C A A G U U G U A U _ G U A G A _ G A _ _ G G U _ A _ U C _ G G G _ C miR-20 _ U _ A C A C G G A G A A A U U A C U G C U A U C ◮ U U U A Cleavage II: Dicer G G C ◮ mature miRNA (miRNAs) Maturation of miRNAs G C U A ◮ C G primary-precursor micro RNA A U G G A G A U U A A U (pri-miRNA) A U U A G C U G C A U ◮ A G Cleavage I: Drosha A U A U G C U A G C ◮ C G precursor miRNA (pre-miRNAs) U G U A A A C G A U G G ◮ U A export to cytoplasm (exportin-5) G C C G A U G C GU A ◮ A U Cleavage II: Dicer G C U AU G C A G U U ◮ mature miRNA (miRNAs) A U G Maturation of miRNAs ◮ primary-precursor micro RNA 5’ A C T (pri-miRNA) G C A ◮ Cleavage I: Drosha G T G A ◮ precursor miRNA (pre-miRNAs) A G G ◮ C export to cytoplasm (exportin-5) A C T T ◮ G Cleavage II: Dicer T 3’ ◮ mature miRNA (miRNAs) Functions of miRNAs Cytoplasm: post-transcriptional gene scilencing (PTGS) ◮ mRNA degradation (RNAi) ◮ translational repression Nucleus: transcriptional gene silencing (TGS) ◮ DNA methylation ◮ heterochromatin remodelling histone methylation Nucleus: transcriptional gene activation (RNAa) ? ◮ binding to promoter regions Functions of miRNAs Cytoplasm: post-transcriptional gene scilencing (PTGS) ◮ mRNA degradation (RNAi) ◮ translational repression Nucleus: transcriptional gene silencing (TGS) ◮ DNA methylation ◮ heterochromatin remodelling histone methylation Nucleus: transcriptional gene activation (RNAa) ? ◮ binding to promoter regions Functions of miRNAs Cytoplasm: post-transcriptional gene scilencing (PTGS) ◮ mRNA degradation (RNAi) ◮ translational repression Nucleus: transcriptional gene silencing (TGS) ◮ DNA methylation ◮ heterochromatin remodelling histone methylation Nucleus: transcriptional gene activation (RNAa) ? ◮ binding to promoter regions Evolutionary origin of prominent ncRNA families Chordata Craniata Y RNA7SK ? U7 Cephalochordata Metazoa RNAse MRP Urochordata telomerase RNA most snRNAs Echinodermata vault RNAs ? Hemichordata Eukarya Protostomia Choanoflagellata Fungi snoRNA C/D snoRNA H/ACA Microsporidia Alveolates Stramenophiles Rhodophyta Green Plants other protists LUCA Archea rRNA Bacteria gRNA in Kinetoplastids only tRNA microRNA in multicellular animals and plants only ? RNAseP tmRNA 7SL/SRP small bacterial RNAs Molecular Evolution of selected miRNAs mir-10, mir196, iab-4 in the Hox gene mir-17 cluster cluster I−B A A A A A I−1 I−A B B B B B I−X I−C C C C C C ? D D D D D mir−196 II II−D Danio rerio Tetraodontiformes Latimeria Mammalia Heterodontus mir−10 iab4 Mammalia Teleostei A A I B B C C II D D Deletions ancestral teleost ancestral sarcopterygian 20 is copy of 17 93 is copy of 17 cluster duplication Branchiostoma ? A 18 is copy of 17 B Petromyzon marinus C ancestral gnathostome 18 deletion D 17 19 Cenorhabditis briggsae Cenorhabditis elegans Tribolium Apis mellifera Anopheles Drosophila 20 92 19b ancestral vertebrate 19b is copy of 19 106b Strongylocentrotus Ciona 93 19−3 25 Tanzer and Stadler. J Mol Biol. 2004; 339:327-35 Tanzer et al. J Exp Zoolog B Mol Dev Evol. 2005; 304:75-85 Expansion of The Metazoan MicroRNA Repertoire Sm Cb Ce Am Tc Bm Ag D.sp. Sp Od Ci Cs Dr Tn Tr Xt Gg MdRn Mm Bt Cf Pt Hs 4 44 23 1 2 2 6 1 2 tandem 2 dupl. 4 1 1 40 6 4 1 5 1 1 non-local 40 2 3 1 1 dupl. 71 13 1 1 2 56 24 11 1 1 innovations 1 0 1 18 1 1 Hertel et al., BMC Genomics.2006;7:25 Expansion of The Metazoan MicroRNA Repertoire Dr Tn Tr Xt Gg MdRn Mm Bt Cf Pt Hs tandem 6 1 dupl. 2 2 40 6 4 non-local dupl. 1 5 1 1 40 2 3 1 1 2 innovations 56 24 11 Hertel et al., BMC Genomics.2006;7:25 Genomic Complexity Mattick JS, The Journal of Experimental Biology 210, 1526-1547 MicroRNAs in Developmet Sm Cb Ce Am Tc Bm Ag D.sp.
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