Abstract
The clustering propensity of microRNA genes is a common biological phenomenon in various animal and plant species. To gain novel insight into genomic organization and potential functional heterogeneities of miRNA clusters in vertebrates from a genome scale, we used large scale data and presented a comprehensive analysis to examine various features of genomic organization of miRNA clusters across seven vertebrates by a combination of comparative genomics and bioinformatics approaches. The results of pair-wise distance analysis of same-strand consecutive miRNAs suggested that the fractions of the miRNA gene pairs are higher at relatively short pair-wise distances than those of protein-coding genes and other non-coding RNA genes. Especially relatively small number of miRNAs is more clustered at very short pair-wise distances than expected at random. We further observed significant difference between real miRNA clusters and randomly organized clusters for different aspects, including higher overlap of target genes, fewer seed types and significant enrichment in diseases. However, the extent of these features of clustered miRNAs has a different tendency and largely depends on inter-miRNA distances because of diverse clustering propensity of miRNAs in vertebrates, suggesting that this cooperated function or cooperative effects between miRNAs in clusters perhaps be affected by inter-miRNA distances.
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References
Carthew RW, Sontheimer EJ (2009) Origins and Mechanisms of miRNAs and siRNAs. Cell 136(4):642–655
Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297
Li L, Xu J, Yang D, Tan X, Wang H (2011) Computational approaches for microRNA studies: a review. Mamm Genome 21(1–2):1–12
Mendes ND, Freitas AT, Sagot MF (2009) Current tools for the identification of miRNA genes and their targets. Nucleic Acids Res 37(8):2419–2433
Wilbert ML, Yeo GW (2011) Genome-wide approaches in the study of microRNA biology. Wiley Interdiscip Rev Syst Biol Med 3. doi:10.1002/wsbm.128
Carrington JC, Ambros V (2003) Role of microRNAs in plant and animal development. Science 301(5631):336–338
Engels BM, Hutvagner G (2006) Principles and effects of microRNA-mediated post-transcriptional gene regulation. Oncogene 25(46):6163–6169
Chi SW, Zang JB, Mele A, Darnell RB (2009) Argonaute HITS-CLIP decodes microRNA–mRNA interaction maps. Nature 460(7254):479–486
Zhou M, Wang Q, Sun J, Li X, Xu L, Yang H, Shi H, Ning S, Chen L, Li Y, He T, Zheng Y (2009) In silico detection and characteristics of novel microRNA genes in the Equus caballus genome using an integrated ab initio and comparative genomic approach. Genomics 94(2):125–131
Yue J, Sheng Y, Orwig KE (2008) Identification of novel homologous microRNA genes in the rhesus macaque genome. BMC Genomics 9:8
Lagos-Quintana M, Rauhut R, Meyer J, Borkhardt A, Tuschl T (2003) New microRNAs from mouse and human. RNA 9(2):175–179
Kaczkowski B, Torarinsson E, Reiche K, Havgaard JH, Stadler PF, Gorodkin J (2009) Structural profiles of human miRNA families from pairwise clustering. Bioinformatics 25(3):291–294
He PA, Nie Z, Chen J, Chen J, Lv Z, Sheng Q, Zhou S, Gao X, Kong L, Wu X, Jin Y, Zhang Y (2008) Identification and characteristics of microRNAs from Bombyx mori. BMC Genomics 9:248
Baev V, Daskalova E, Minkov I (2009) Computational identification of novel microRNA homologs in the chimpanzee genome. Comput Biol Chem 33(1):62–70
Zhang Y, Zhang R, Su B (2009) Diversity and evolution of MicroRNA gene clusters. Sci China C Life Sci 52(3):261–266
Guo L, Lu Z (2011) Global expression analysis of miRNA gene cluster and family based on isomiRs from deep sequencing data. Comput Biol Chem 34(3):165–171
Chhabra R, Dubey R, Saini N (2010) Cooperative and individualistic functions of the microRNAs in the miR-23a–27a–24-2 cluster and its implication in human diseases. Mol Cancer 9:232
Griffiths-Jones S, Saini HK, van Dongen S, Enright AJ (2008) miRBase: tools for microRNA genomics. Nucleic Acids Res 36 (Database issue):D154–D158
Kuhn RM, Karolchik D, Zweig AS, Wang T, Smith KE, Rosenbloom KR, Rhead B, Raney BJ, Pohl A, Pheasant M, Meyer L, Hsu F, Hinrichs AS, Harte RA, Giardine B, Fujita P, Diekhans M, Dreszer T, Clawson H, Barber GP, Haussler D, Kent WJ (2009) The UCSC Genome Browser Database: update 2009. Nucleic Acids Res 37 (Database issue):D755–D761
Ruepp A, Kowarsch A, Schmidl D, Buggenthin F, Brauner B, Dunger I, Fobo G, Frishman G, Montrone C, Theis FJ (2010) PhenomiR: a knowledgebase for microRNA expression in diseases and biological processes. Genome Biol 11(1):R6
Altuvia Y, Landgraf P, Lithwick G, Elefant N, Pfeffer S, Aravin A, Brownstein MJ, Tuschl T, Margalit H (2005) Clustering and conservation patterns of human microRNAs. Nucleic Acids Res 33(8):2697–2706
Jiang QH, Hao YY, Wang GH, Juan LR, Zhang TJ (2010) Prioritization of disease microRNAs through a human phenome-microRNAome network. BMC Syst Biol 4(Supp l):S2
Lee DY, Deng Z, Wang CH, Yang BB (2007) MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression. Proc Natl Acad Sci USA 104(51):20350–20355
Lu M, Zhang Q, Deng M, Miao J, Guo Y, Gao W, Cui Q (2008) An analysis of human microRNA and disease associations. PLoS One 3(10):e3420
Friedman RC, Farh KK, Burge CB, Bartel DP (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19(1):92–105
Dehal P, Boore JL (2005) Two rounds of whole genome duplication in the ancestral vertebrate. PLoS Biol 3(10):e314
Kassahn KS, Dang VT, Wilkins SJ, Perkins AC, Ragan MA (2009) Evolution of gene function and regulatory control after whole-genome duplication: comparative analyses in vertebrates. Genome Res 19(8):1404–1418
Donoghue PC, Purnell MA (2005) Genome duplication, extinction and vertebrate evolution. Trends Ecol Evol 20(6):312–319
Heimberg AM, Sempere LF, Moy VN, Donoghue PC, Peterson KJ (2008) MicroRNAs and the advent of vertebrate morphological complexity. Proc Natl Acad Sci USA 105(8):2946–2950
Hertel J, Lindemeyer M, Missal K, Fried C, Tanzer A, Flamm C, Hofacker IL, Stadler PF (2006) The expansion of the metazoan microRNA repertoire. BMC Genomics 7:25
Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S, Yatabe Y, Kawahara K, Sekido Y, Takahashi T (2005) A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 65(21):9628–9632
Yu J, Wang F, Yang GH, Wang FL, Ma YN, Du ZW, Zhang JW (2006) Human microRNA clusters: genomic organization and expression profile in leukemia cell lines. Biochem Biophys Res Commun 349(1):59–68
Xu J, Wong C (2008) A computational screen for mouse signaling pathways targeted by microRNA clusters. RNA 14(7):1276–1283
Yuan X, Liu C, Yang P, He S, Liao Q, Kang S, Zhao Y (2009) Clustered microRNAs’ coordination in regulating protein–protein interaction network. BMC Syst Biol 3:65
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Jie Sun and Hai-ping Liu contributed equally to this work.
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Sun, J., Liu, Hp., Deng, Je. et al. Systematic analysis of genomic organization and heterogeneities of miRNA cluster in vertebrates. Mol Biol Rep 39, 5143–5149 (2012). https://doi.org/10.1007/s11033-011-1310-4
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DOI: https://doi.org/10.1007/s11033-011-1310-4