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Diversity and evolution of MicroRNA gene clusters

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Abstract

microRNA (miRNA) gene clusters are a group of miRNA genes clustered within a proximal distance on a chromosome. Although a large number of miRNA clusters have been uncovered in animal and plant genomes, the functional consequences of this arrangement are still poorly understood. Located in a polycistron, the coexpressed miRNA clusters are pivotal in coordinately regulating multiple processes, including embryonic development, cell cycles and cell differentiation. In this review, based on recent progress, we discuss the genomic diversity of miRNA gene clusters, the coordination of expression and function of the clustered miRNAs, and the evolutionarily adaptive processes with gain and loss of the clustering miRNA genes mediated by duplication and transposition events.

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References

  1. Dennis C. The brave new world of RNA. Nature, 2002, 418: 122–124 12110860, 10.1038/418122a, 1:CAS:528:DC%2BD38XltFGmtb0%3D

    Article  PubMed  CAS  Google Scholar 

  2. Lee Y, Lee Y, Kim M, et al. MicroRNA genes are transcribed by RNA polymerase II. EMBO, 2004, 23: 4051–4060 10.1038/sj.emboj.7600385, 1:CAS:528:DC%2BD2cXotlCrsrs%3D

    Article  CAS  Google Scholar 

  3. Borchert G M, Lanier W, Davidson1 B L. RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol, 2006, 13: 1097–1101 17099701, 10.1038/nsmb1167, 1:CAS:528:DC%2BD28Xht1KrurnO

    Article  PubMed  CAS  Google Scholar 

  4. Bartel D P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 2004, 116: 281–297 14744438, 10.1016/S0092-8674(04)00045-5, 1:CAS:528:DC%2BD2cXhtVals7o%3D

    Article  PubMed  CAS  Google Scholar 

  5. Han J, Lee1 Y, Yeom K H, et al. Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell, 2006, 125: 887–901 16751099, 10.1016/j.cell.2006.03.043, 1:CAS:528:DC%2BD28Xls1Shtr4%3D

    Article  PubMed  CAS  Google Scholar 

  6. Bohnsack M T, Czaplinski K, Gorlich D. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA, 2004, 10: 185–191 14730017, 10.1261/rna.5167604, 1:CAS:528:DC%2BD2cXpsVSitg%3D%3D

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  7. Brennecke J, Stark A, Russell R B, et al. Principles of microRNA-target recognition. PLoS Biol, 2005, 3(3):e85 15723116, 10.1371/journal.pbio.0030085

    Article  PubMed Central  PubMed  Google Scholar 

  8. Lai E C. Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation. Nat Genet, 2002, 30: 363–364 11896390, 10.1038/ng865, 1:CAS:528:DC%2BD38Xisl2lsL8%3D

    Article  PubMed  CAS  Google Scholar 

  9. Selbach M, Schwanhausser B, Thierfelder N, et al. Widespread changes in protein synthesis induced by microRNAs. Nature, 2008, 455(7209): 58–63 18668040, 10.1038/nature07228, 1:CAS:528:DC%2BD1cXhtVKrsbnK

    Article  PubMed  CAS  Google Scholar 

  10. Krek A, Grun D, Poy M N, et al. Combinatorial microRNA target predictions. Nat Genet, 2005, 37: 495–500 15806104, 10.1038/ng1536, 1:CAS:528:DC%2BD2MXjsF2ksrw%3D

    Article  PubMed  CAS  Google Scholar 

  11. Reinhart B J, Slack F J, Basson M, et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature, 2000, 403: 901–906 10706289, 10.1038/35002607, 1:CAS:528:DC%2BD3cXhs1Ors74%3D

    Article  PubMed  CAS  Google Scholar 

  12. Lee R C, Feinbaum R L, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell, 1993, 75: 843–854 8252621, 10.1016/0092-8674(93)90529-Y, 1:CAS:528:DyaK2cXpslGqtA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  13. Felli N, Fontana L, Pelosi E, et al. MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. Proc Natl Acad Sci USA, 2005, 102: 18081–18086 16330772, 10.1073/pnas.0506216102, 1:CAS:528:DC%2BD2MXhtlersr3K

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  14. Ambros V. The functions of animal microRNAs. Nature, 2004, 431: 350–355 15372042, 10.1038/nature02871, 1:CAS:528:DC%2BD2cXnsFaiu7g%3D

    Article  PubMed  CAS  Google Scholar 

  15. Huang J L, Wang F X, Argyris E, et al. Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes. Nat Med, 2007, 13: 1241–1247 17906637, 10.1038/nm1639, 1:CAS:528:DC%2BD2sXhtFagsb3L

    Article  PubMed  CAS  Google Scholar 

  16. Van R E, Sutherland L B, Qi X, et al. Control of stress-dependent cardiac growth and gene expression by a microRNA. Science, 2007, 316: 575–579 10.1126/science.1139089

    Article  Google Scholar 

  17. Esquela-Kerscher A, Slack F J. Oncomirs — microRNAs with a role in cancer. Nat Rev Cancer, 2006, 6: 259–269 16557279, 10.1038/nrc1840, 1:CAS:528:DC%2BD28XivVyqtrs%3D

    Article  PubMed  CAS  Google Scholar 

  18. Chang T C, Mendell J T. microRNAs in vertebrate physiology and human disease. Annu Rev Genom Human Genet, 2007, 8: 215–239 10.1146/annurev.genom.8.080706.092351, 1:CAS:528:DC%2BD2sXht1WksrrM

    Article  CAS  Google Scholar 

  19. Hébert S S, De Strooper B. miRNAs in neurodegeneration. Science, 2007, 31, 317:1179–1180 10.1126/science.1148530

    Article  Google Scholar 

  20. Yang B, Lin H, Xiao J, et al. The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nat Med, 2007, 13: 486–491 17401374, 10.1038/nm1569, 1:CAS:528:DC%2BD2sXjvVaqurs%3D

    Article  PubMed  CAS  Google Scholar 

  21. Lagos-Quintana M, Rauhut R, Meyer J, et al. New microRNAs from mouse and human. RNA, 2003, 9: 175–179 12554859, 10.1261/rna.2146903, 1:CAS:528:DC%2BD3sXhtVWnu7o%3D

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  22. Lai E C, Tomancak P, Williams R W, et al. Computational identification of Drosophila microRNA genes. Genome Biol, 2003, 4: R42 12844358, 10.1186/gb-2003-4-7-r42

    Article  PubMed Central  PubMed  Google Scholar 

  23. Lewin B. Genes VIII. New Jersey: Pearson Education Inc, 2004

    Google Scholar 

  24. Altuvia Y, Landgraf P, Lithwick G, et al. Clustering and conservation patterns of human microRNAs. Nucleic Acids Res, 2005, 33: 2697–2706 15891114, 10.1093/nar/gki567, 1:CAS:528:DC%2BD2MXktF2nsLc%3D

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  25. Megraw M, Sethupathy P, Corda B, et al. miRGen: A database for the study of animal microRNA genomic organization and function. Nucleic Acids Res, 2007, 35: D149–D155 17108354, 10.1093/nar/gkl904, 1:CAS:528:DC%2BD2sXivFKitA%3D%3D

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  26. Tang G Q, Maxwell E S. Xenopus microRNA genes are predominantly located within introns and are differentially expressed in adult frog tissues via post-transcriptional regulation. Genome Res, 2008, 18: 104–112 18032731, 10.1101/gr.6539108, 1:CAS:528:DC%2BD1cXnvF2g

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  27. Mendell J T. miRiad roles for the miR-17–92 cluster in development and disease. Cell, 2008, 133: 217–222 18423194, 10.1016/j.cell.2008.04.001, 1:CAS:528:DC%2BD1cXltlWnurY%3D

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. Lau N, Lim L, Weinstein E, et al. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science, 2001, 294: 858–862 11679671, 10.1126/science.1065062, 1:CAS:528:DC%2BD3MXotVChurw%3D

    Article  PubMed  CAS  Google Scholar 

  29. Pasquinelli A, Reinhart B, Slack F, et al. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature, 2000, 408: 86–89 11081512, 10.1038/35040556, 1:CAS:528:DC%2BD3cXotVaks70%3D

    Article  PubMed  CAS  Google Scholar 

  30. John B, Enright A J, Aravin A, et al. Human MicroRNA targets. PLoS Biol, 2004, 2(11): e363 15502875, 10.1371/journal.pbio.0020363

    Article  PubMed Central  PubMed  Google Scholar 

  31. Poy M N, Eliasson L, Krutzfeldt J, et al. A pancreatic islet-specific microRNA regulates insulin secretion. Nature, 2004, 432: 226–230 15538371, 10.1038/nature03076, 1:CAS:528:DC%2BD2cXpsF2gt78%3D

    Article  PubMed  CAS  Google Scholar 

  32. Cullen B R. Transcription and processing of human microRNA precursors. Mol Cell, 2004, 16: 861–865 15610730, 10.1016/j.molcel.2004.12.002, 1:CAS:528:DC%2BD2MXjvVSqtA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  33. Baskerville S, Bartel D P. Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA, 2005, 11: 241–247 15701730, 10.1261/rna.7240905, 1:CAS:528:DC%2BD2MXhvVCjt7o%3D

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  34. Lu J, Fu Y, Kumar S, et al. Adaptive evolution of newly emerged microRNA genes in Drosophila. Mol Biol Evol, 2008, 25: 929–938 18296702, 10.1093/molbev/msn040, 1:CAS:528:DC%2BD1cXlvVKhu74%3D

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  35. Yu J, Wang F, Yang G H, et al. Human microRNA clusters: Genomic organization and expression profile in leukemia cell lines. Biochem Biophys Res Commun, 2006, 349: 59–68 16934749, 10.1016/j.bbrc.2006.07.207, 1:CAS:528:DC%2BD28XpsVKqsLs%3D

    Article  PubMed  CAS  Google Scholar 

  36. Xu J Z, I Wong C W. A computational screen for mouse signaling pathways targeted by microRNA clusters. RNA, 2008, 14: 1276–1283 18511500, 10.1261/rna.997708, 1:CAS:528:DC%2BD1cXot1amt7s%3D

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  37. Liu Q, Fu H, Sun F, et al. miR-16 family induces cell cycle arrest by regulating multiple cell cycle genes. Nucleic Acids Res, 2008, 36: 5391–5404 18701644, 10.1093/nar/gkn522, 1:CAS:528:DC%2BD1cXhtFWhs7nO

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  38. Friggi-Grelin F, Lavenant-Staccini L, Therond P. Control of antagonistic components of the hedgehog signaling pathway by microRNAs in Drosophila. Genetics, 2008, 179: 429–439 18493062, 10.1534/genetics.107.083733, 1:CAS:528:DC%2BD1cXnsl2qtrc%3D

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  39. Leaman D, Chen P Y, Fak J, et al. Antisense-mediated depletion reveals essential and specific functions of microRNAs in Drosophila development. Cell, 2005, 121: 1097–1108 15989958, 10.1016/j.cell.2005.04.016, 1:CAS:528:DC%2BD2MXmtF2ntr0%3D

    Article  PubMed  CAS  Google Scholar 

  40. Ohler U, Yekta S, Lim L P, et al. Patterns of flanking sequence conservation and a characteristic upstream motif for microRNA gene identification. RNA, 2004, 10: 1309–1322 15317971, 10.1261/rna.5206304, 1:CAS:528:DC%2BD2cXnsVejsLY%3D

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  41. Berezikov E, Guryev V, van de Belt J, et al. Phylogenetic shadowing and computational identification of human microRNA genes. Cell, 2005, 120: 21–24 15652478, 10.1016/j.cell.2004.12.031, 1:CAS:528:DC%2BD2MXot1ChsQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  42. Li X, Yang S, Peng L X, et al. Origin and evolution of new genes. Chinese Science Bulletin, 2004, 49(13): 1219–1225 (in Chinese) 10.1360/03wb0215

    Article  Google Scholar 

  43. Zhang R, Peng Y, Wang W, et al. Rapid evolution of an X-linked microRNA cluster in primates. Genome Res, 2007, 17: 612–617 17416744, 10.1101/gr.6146507, 1:CAS:528:DC%2BD2sXltF2itrs%3D

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  44. Su B, Zhang R. MicroRNA evolution in the human genome. Encyclopedia of Life Sciences, 2008, DOI: 10.1002/9780470015902. a0020788

  45. Tanzer A, Stadler P F. Molecular evolution of a microRNA cluster. Mol Biol, 2004, 339: 327–335 10.1016/j.jmb.2004.03.065, 1:CAS:528:DC%2BD2cXjsl2ns78%3D

    Article  CAS  Google Scholar 

  46. Hertel J, Lindemeyer M, Missal K, et al. The expansion of the metazoan microRNA repertoire. BMC Genomics, 2006, 7: 25 16480513, 10.1186/1471-2164-7-25

    Article  PubMed Central  PubMed  Google Scholar 

  47. Li A, Mao L. Evolution of plant microRNA gene families. Cell Res, 2006, 17: 212–218 1:CAS:528:DC%2BD28XhtFSgtb3L

    CAS  Google Scholar 

  48. Maher C, Stein L, Ware D. Evolution of Arabidopsis microRNA families through duplication events. Genome Res, 2006, 16: 510–519 16520461, 10.1101/gr.4680506, 1:CAS:528:DC%2BD28Xjs12ju78%3D

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  49. Piriyapongsa J, Marino-Ramirez L, Jordan I K. Origin and evolution of human microRNAs from transposable elements. Genetics, 2007, 176: 1323–1337 17435244, 10.1534/genetics.107.072553, 1:CAS:528:DC%2BD2sXovVOqs7k%3D

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  50. Zhang R, Wang Y Q, Su B. Molecular evolution of a primate-specific microRNA family. Mol Biol Evol, 2008, 25: 1493–1502 18417486, 10.1093/molbev/msn094, 1:CAS:528:DC%2BD1cXotlKgt7o%3D

    Article  PubMed  CAS  Google Scholar 

  51. Lu J, Shen Y, Wu Q, et al. The birth and death of microRNA genes in Drosophila. Nat Genet, 2008, 40: 351–355 18278047, 10.1038/ng.73, 1:CAS:528:DC%2BD1cXisVKhtr8%3D

    Article  PubMed  CAS  Google Scholar 

  52. Richly E, Leister D. NUMTs in sequenced eukaryotic genomes. Mol Biol Evol, 2004, 21: 1081–1084 15014143, 10.1093/molbev/msh110, 1:CAS:528:DC%2BD2cXksVymurc%3D

    Article  PubMed  CAS  Google Scholar 

  53. Lercher M J, Pál C. Integration of horizontally transferred genes into regulatory interaction networks takes many million years. Mol Biol Evol, 2008, 25: 559–567 18158322, 10.1093/molbev/msm283, 1:CAS:528:DC%2BD1cXjt1Cltb8%3D

    Article  PubMed  CAS  Google Scholar 

  54. Bartel D P, Chen C Z. Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs. Nat Rev Genet, 2004, 5: 396–400 15143321, 10.1038/nrg1328, 1:CAS:528:DC%2BD2cXjsl2hsr0%3D

    Article  PubMed  CAS  Google Scholar 

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  1. State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China

    YanFeng Zhang, Rui Zhang & Bing Su

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  1. YanFeng Zhang
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  2. Rui Zhang
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Correspondence to Bing Su.

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Supported by State Key Program of National Natural Science of China(Grant No. 306300130)

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Zhang, Y., Zhang, R. & Su, B. Diversity and evolution of MicroRNA gene clusters. SCI CHINA SER C 52, 261–266 (2009). https://doi.org/10.1007/s11427-009-0032-5

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