Abstract
Stem-bulge RNAs (sbRNAs) are a group of small, functionally yet uncharacterized noncoding RNAs first described in C. elegans, with a few homologous sequences postulated in C. briggsae. In this study, we report on a comprehensive survey of this ncRNA family in the phylum Nematoda. Employing homology search strategies based on both sequence and secondary structure models and a computational promoter screen we identified a total of 240 new sbRNA homologs. For the majority of these loci we identified both promoter regions and transcription termination signals characteristic for pol-III transcripts. Sequence and structure comparison with known RNA families revealed that sbRNAs are homologs of vertebrate Y RNAs. Most of the sbRNAs show the characteristic Ro protein binding motif, and contain a region highly similar to a functionally required motif for DNA replication previously thought to be unique to vertebrate Y RNAs. The single Y RNA that was previously described in C. elegans, however, does not show this motif, and in general bears the hallmarks of a highly derived family member.
Similar content being viewed by others
References
Abad P, Gouzy J, Aury JM, Castagnone-Sereno P, Danchin EG, Deleury E, Perfus-Barbeoch L, Anthouard V, Artiguenave F, Blok VC, Caillaud MC, Coutinho PM, Dasilva C, De Luca F, Deau F, Esquibet M, Flutre T, Goldstone JV, Hamamouch N, Hewezi T, Jaillon O, Jubin C, Leonetti P, Magliano M, Maier TR, Markov GV, McVeigh P, Pesole G, Poulain J, Robinson-Rechavi M, Sallet E, Ségurens B, Steinbach D, Tytgat T, Ugarte E, van Ghelder C, Veronico P, Baum TJ, Blaxter M, Bleve-Zacheo T, Davis EL, Ewbank JJ, Favery B, Grenier E, Henrissat B, Jones JT, Laudet V, Maule AG, Quesneville H, Rosso MN, Schiex T, Smant G, Weissenbach J, Wincker P (2008) Genome sequence of the metazoan plant-parasitic nematode Meloidogyne incognita. Nat Biotechnol 26:909–915
Aerts S, Van Loo P, Thijs G, Moreau Y, De Moor B (2003) Computational detection of cis-regulatory modules. Bioinformatics 19:5–14
Aftab MN, He H, Skogerbø G, Chen R (2008) Microarray analysis of ncRNA expression patterns in Caenorhabditis elegans after RNAi against snoRNA associated proteins. BMC Genom 9:278–278
Barrière A, Yang SP, Pekarek E, Thomas CG, Haag ES, Ruvinsky I (2009) Detecting heterozygosity in shotgun genome assemblies: lessons from obligately outcrossing nematodes. Genome Res 19:470–480
Bernhart SH, Hofacker IL, Will S, Gruber AR, Stadler PF (2008) RNAalifold: improved consensus structure prediction for RNA alignments. BMC Bioinform 9:474–474
Blaxter ML, De Ley P, Garey JR, Liu LX, Scheldeman P, Vierstraete A, Vanfleteren JR, Mackey LY, Dorris M, Frisse LM, Vida JT, Thomas WK (1998) A molecular evolutionary framework for the phylum Nematoda. Nature 392:71–75
Chen X, Wurtmann EJ, Van Batavia J, Zybailov B, Washburn MP, Wolin SL (2007) An ortholog of the Ro autoantigen functions in 23s rRNA maturation in D. radiodurans. Genes Dev 21:1328–1339
Chilton NB, Huby-Chilton F, Gasser RB, Beveridge I (2006) The evolutionary origins of nematodes within the order Strongylida are related to predilection sites within hosts. Mol Phylogenet Evol 40:118–128
Christov CP, Gardiner TJ, Szüts D, Krude T (2006) Functional requirement of noncoding Y RNAs for human chromosomal DNA replication. Mol Cell Biol 26:6993–7004
Christov CP, Trivier E, Krude T (2008) Noncoding human Y RNAs are overexpressed in tumours and required for cell proliferation. Br J Cancer 98:981–988
Crooks GE, Hon G, Chandonia JM, Brenner SE (2004) WebLogo: a sequence logo generator. Genome Res 14:1188–1190
Dávila López M, Rosenblad MA, Samuelsson T (2008) Computational screen for spliceosomal RNA genes aids in defining the phylogenetic distribution of major and minor spliceosomal components. Nucleic Acids Res 36:3001–3010
Deng W, Zhu X, Skogerbø G, Zhao Y, Fu Z, Wang Y, He H, Cai L, Sun H, Liu C, Li B, Bai B, Wang J, Jia D, Sun S, He H, Cui Y, Wang Y, Bu D, Chen R (2006) Organization of the Caenorhabditis elegans small non-coding transcriptome: genomic features, biogenesis, and expression. Genome Res 16:20–29
Gardiner TJ, Christov CP, Langley AR, Krude T (2009) A conserved motif of vertebrate Y RNAs essential for chromosomal DNA replication. RNA 15:1375–1385
Green CD, Long KS, Shi H, Wolin SL (1998) Binding of the 60-kDa Ro autoantigen to Y RNAs: evidence for recognition in the major groove of a conserved helix. RNA 4:750–765
Griffiths-Jones S (2005) RALEE–RNA alignment editor in emacs. Bioinformatics 21:257–259
Gruber AR, Kilgus C, Mosig A, Hofacker IL, Hennig W, Stadler PF (2008) Arthropod 7SK RNA. Mol Biol Evol 25:1923–1930
Guffanti E, Corradini R, Ottonello S, Dieci G (2004) Functional dissection of RNA polymerase III termination using a peptide nucleic acid as a transcriptional roadblock. J Biol Chem 279:20708–20716
Gunnery S, Ma Y, Mathews MB (1999) Termination sequence requirements vary among genes transcribed by RNA polymerase III. J Mol Biol 286:745–757
Hernandez N (2001) Small nuclear RNA genes: a model system to study fundamental mechanisms of transcription. J Biol Chem 276:26733–26736
Hertel J, Hofacker IL, Stadler PF (2008) SnoReport: computational identification of snoRNAs with unknown targets. Bioinformatics 24:158–164
Hertel J, de Jong D, Marz M, Rose D, Tafer H, Tanzer A, Schierwater B, Stadler PF (2009) Non-coding RNA annotation of the genome of Trichoplax adhaerens. Nucleic Acids Res 37:1602–1615
Hofacker IL, Fekete M, Stadler PF (2002) Secondary structure prediction for aligned RNA sequences. J Mol Biol 319:1059–1066
Hogg RJ, Collins K (2008) Structured non-coding RNAs and the RNP Renaissance. Curr Opin Chem Biol 12:684–689
Kaczkowski B, Torarinsson E, Reiche K, Havgaard JH, Stadler PF, Gorodkin J (2009) Structural profiles of miRNA families from pairwise clustering. Bioinformatics 25:291–294
Kamath RS, Fraser AG, Dong Y, Poulin G, Durbin R, Gotta M, Kanapin A, Le Bot N, Moreno S, Sohrmann M, Welchman DP, Zipperlen P, Ahringer J (2003) Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421:231–237
Kel AE, Gössling E, Reuter I, Cheremushkin E, Kel-Margoulis OV, Wingender E (2003) MATCH: a tool for searching transcription factor binding sites in DNA sequences. Nucleic Acids Res 31:3576–3579
Li T, He H, Wang Y, Zheng H, Skogerbø G, Chen R (2008) In vivo analysis of Caenorhabditis elegans noncoding RNA promoter motifs. BMC Mol Biol 9:71–71
Marz M, Kirsten T, Stadler PF (2008) Evolution of spliceosomal snRNA genes in metazoan animals. J Mol Evol 67:594–607
Missal K, Zhu X, Rose D, Deng W, Skogerbø G, Chen R, Stadler PF (2006) Prediction of structured non-coding RNAs in the genomes of the nematodes Caenorhabditis elegans and Caenorhabditis briggsae. J Exp Zool B Mol Dev Evol 306:379–392
Mitreva M, Blaxter ML, Bird DM, McCarter JP (2005) Comparative genomics of nematodes. Trends Genet 21:573–581
Mosig A, Guofeng M, Stadler BM, Stadler PF (2007a) Evolution of the vertebrate Y RNA cluster. Theory Biosci 126:9–14
Mosig A, Chen JL, Stadler PF (2007b) Homology search with fragmented nucleic acid sequence patterns. In: Giancarlo R, Hannenhalli S (eds) Algorithms in bioinformatics (WABI 2007), Volume 4645 of Lecture Notes in Computer Science. Springer Verlag, Berlin, Heidelberg, pp 335–345
Pagano A, Castelnuovo M, Tortelli F, Ferrari R, Dieci G, Cancedda R (2007) New small nuclear RNA gene-like transcriptional units as sources of regulatory transcripts. PLoS Genet 3:e1
Ploner A, Ploner C, Lukasser M, Niederegger H, Hüttenhofer A (2009) Methodological obstacles in knocking down small noncoding RNAs. RNA 15:1797–1804
Perreault J, Perreault JP, Boire G (2007) Ro-associated Y RNAs in metazoans: evolution and diversification. Mol Biol Evol 24:1678–1689
Sönnichsen B, Koski LB, Walsh A, Marschall P, Neumann B, Brehm M, Alleaume AM, Artelt J, Bettencourt P, Cassin E, Hewitson M, Holz C, Khan M, Lazik S, Martin C, Nitzsche B, Ruer M, Stamford J, Winzi M, Heinkel R, Röder M, Finell J, Häntsch H, Jones SJ, Jones M, Piano F, Gunsalus KC, Oegema K, Gönczy P, Coulson A, Hyman AA, Echeverri CJ (2005) Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans. Nature 434:462–469
Stein AJ, Fuchs G, Fu C, Wolin SL, Reinisch KM (2005) Structural insights into RNA quality control: the Ro autoantigen binds misfolded RNAs via its central cavity. Cell 121:529–539
Sudhaus W, Kiontke K (2007) Comparison of the cryptic nematode species Caenorhabditis brenneri sp. n. and C. remanei (Nematoda: Rhabditidae) with the stem species pattern of the Caenorhabditis elegans group. Zootaxa 1456:45–62
Tanzer A, Stadler PF (2004) Molecular evolution of a microRNA cluster. J Mol Biol 339:327–335
Tanzer A, Stadler PF (2006) Evolution of MicroRNAs. In: Ying SY (ed) MicroRNA protocols. Humana Press, Totowa, NJ, pp 335–350
Thomas J, Lea K, Zucker-Aprison E, Blumenthal T (1990) The spliceosomal snRNAs of Caenorhabditis elegans. Nucleic Acids Res 18:2633–2642
Van Horn DJ, Eisenberg D, O’Brien CA, Wolin SL (1995) Caenorhabditis elegans embryos contain only one major species of Ro RNP. RNA 1:293–303
Waterhouse AM, Procter JB, Martin DM, Clamp M, Barton GJ (2009) Jalview Version 2—a multiple sequence alignment editor and analysis workbench. Bioinformatics 25:1189–1191
Will S, Reiche K, Hofacker IL, Stadler PF, Backofen R (2007) Inferring noncoding RNA families and classes by means of genome-scale structure-based clustering. PLoS Comput Biol 3:e65
Zemann A, op de Bekke A, Kiefmann M, Brosius J, Schmitz J (2006) Evolution of small nucleolar RNAs in nematodes. Nucleic Acids Res 34:2676–2685
Acknowledgments
This research originated from an RNA Bioinformatics course at the University of Vienna in the fall semester 2008. Subsequently, it was then funded in part by the Austrian GEN-AU projects “Bioinformatics Integration Network III” and “Noncoding RNA”, the AMS Vienna and the DFG under the auspices of the SPPs 1174 “Deep Metazoan Phylogeny” and 1258 “Sensory and Regulatory RNAs”.
Author information
Authors and Affiliations
Corresponding author
Additional information
I. Boria, A. R. Gruber, and A. Tanzer contributed equally to this work.
Electronic supplementary material
An Electronic Supplement located at http://www.bioinf.uni-leipzig.de/Publications/SUPPLEMENTS/09-020/ compiles a list of detected sbRNAs, sequence data, and alignments in machine-readable form.
239_2010_9332_MOESM1_ESM.pdf
Structure evolution of sbRNA loop regions. Gene duplication coincides with duplication of substructures within the loops regions as shown here for members ofthe long sbRNAs residing on C. elegans chromosome V. The ancestral gene of this family possibly consisted of four hairpins. During subsequent gene duplications,individual hairpins were lost. The hairpin B (yellow) shows high sequence similarity to the adjacent hairpin A (green) and probably arose by local duplication of astructural element. A,B,C,D: RNA secondary structures of representatives of each family. family ABCD: Cn4 (A); family AB_D: CeN73_1 (B); family A_CD: Cn8(C); family _BCD: Cr26 (D). (E) hand curated CLUSTAL W multiple sequence alignments including the consensus structure and location of structural motifs. PDF (188 KB)
Rights and permissions
About this article
Cite this article
Boria, I., Gruber, A.R., Tanzer, A. et al. Nematode sbRNAs: Homologs of Vertebrate Y RNAs. J Mol Evol 70, 346–358 (2010). https://doi.org/10.1007/s00239-010-9332-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00239-010-9332-4