miRNA, Biogenesis and Mechanisms of Regulations

Document Type : Review Article

Authors

1 MSc Student, Pediatric Inherited Diseases Research Center, Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Assistant Professor, Pediatric Inherited Diseases Research Center, Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

miRNAs(microRNAs) were discovered in 1993 in Caenorhabditis elegans as one of the most important gene expression regulatory factors. This regulatory role includes many of the important intracellular processes like genesis, differentiation, proliferation and apoptosis. miRNAs are among mRNAs and like them are transcribed by RNA polymerase II and then cap and polyA tail are added to them. The resulted pri-miRNA converts to mature miRNA by two sequential trimming reactions. miRNAs exerts their regulatory effects by translation repression, translation activation and mRNA degradation. miRNAshave an important role in regulation of immune and nervous systems and disorder in their expression can lead to separate disease in both systems.

Keywords

References

  1. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993; 75(5): 843-54.
  2. Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 1993; 75(5): 855-62.
  3. Pasquinelli AE, Reinhart BJ, Slack F, Martindale MQ, Kuroda MI, Maller B, et al. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 2000; 408(6808): 86-9.
  4. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science 2001; 294(5543): 853-8.
  5. Lau NC, Lim LP, Weinstein EG, Bartel DP. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 2001; 294(5543): 858-62.
  6. Lee RC, Ambros V. An extensive class of small RNAs in Caenorhabditis elegans. Science 2001; 294(5543): 862-4.
  7. Reinhart BJ, Weinstein EG, Rhoades MW, Bartel B, Bartel DP. MicroRNAs in plants. Genes Dev 2002; 16(13): 1616-26.
  8. Bentwich I, Avniel A, Karov Y, Aharonov R, Gilad S, Barad O, et al. Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet 2005; 37(7): 766-70.
  9. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005; 120(1): 15-20.
  10. Lim LP, Glasner ME, Yekta S, Burge CB, Bartel DP. Vertebrate microRNA genes. Science 2003; 299(5612): 1540.
  11. Wahid F, Shehzad A, Khan T, Kim YY. MicroRNAs: synthesis, mechanism, function, and recent clinical trials. Biochim Biophys Acta 2010; 1803(11): 1231-43.
  12. Le QJ, Caldas C. Micro-RNAs and breast cancer. Mol Oncol 2010; 4(3): 230-41.
  13. Almeida MI, Reis RM, Calin GA. MicroRNA history: discovery, recent applications, and next frontiers. Mutat Res 2011; 717(1-2): 1-8.
  14. Carthew RW, Sontheimer EJ. Origins and Mechanisms of miRNAs and siRNAs. Cell 2009; 136(4): 642-55.
  15. Bushati N, Cohen SM. microRNA functions. Annu Rev Cell Dev Biol 2007; 23: 175-205.
  16. Kim VN. MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol 2005; 6(5): 376-85.
  17. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116(2): 281-97.
  18. Lu J, Shen Y, Wu Q, Kumar S, He B, Shi S, et al. The birth and death of microRNA genes in Drosophila. Nat Genet 2008; 40(3): 351-5.
  19. Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature 2003; 425(6956): 415-9.
  20. Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ. Processing of primary microRNAs by the Microprocessor complex. Nature 2004; 432(7014): 231-5.
  21. Okamura K, Hagen JW, Duan H, Tyler DM, Lai EC. The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila. Cell 2007; 130(1): 89-100.
  22. Ruby JG, Jan CH, Bartel DP. Intronic microRNA precursors that bypass Drosha processing. Nature 2007; 448(7149): 83-6.
  23. Hock J, Weinmann L, Ender C, Rudel S, Kremmer E, Raabe M, et al. Proteomic and functional analysis of Argonaute-containing mRNA-protein complexes in human cells. EMBO Rep 2007; 8(11): 1052-60.
  24. Zhang L, Ding L, Cheung TH, Dong MQ, Chen J, Sewell AK, et al. Systematic identification of C. elegans miRISC proteins, miRNAs, and mRNA targets by their interactions with GW182 proteins AIN-1 and AIN-2. Mol Cell 2007; 28(4): 598-613.
  25. Peters L, Meister G. Argonaute proteins: mediators of RNA silencing. Mol Cell 2007; 26(5): 611-23.
  26. Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM, Song JJ, et al. Argonaute2 is the catalytic engine of mammalian RNAi. Science 2004; 305(5689): 1437-41.
  27. Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell 2004; 15(2): 185-97.
  28. Okamura K, Ishizuka A, Siomi H, Siomi MC. Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways. Genes Dev 2004; 18(14): 1655-66.
  29. Pillai RS, Artus CG, Filipowicz W. Tethering of human Ago proteins to mRNA mimics the miRNA-mediated repression of protein synthesis. RNA 2004; 10(10): 1518-25.
  30. Vasudevan S, Steitz JA. AU-rich-element-mediated upregulation of translation by FXR1 and Argonaute 2. Cell 2007; 128(6): 1105-18.
  31. Behm-Ansmant I, Rehwinkel J, Doerks T, Stark A, Bork P, Izaurralde E. mRNA degradation by miRNAs and GW182 requires both CCR4:NOT deadenylase and DCP1:DCP2 decapping complexes. Genes Dev 2006; 20(14): 1885-98.
  32. Jakymiw A, Lian S, Eystathioy T, Li S, Satoh M, Hamel JC, et al. Disruption of GW bodies impairs mammalian RNA interference. Nat Cell Biol 2005; 7(12): 1267-74.
  33. Liu J, Rivas FV, Wohlschlegel J, Yates JR, III, Parker R, Hannon GJ. A role for the P-body component GW182 in microRNA function. Nat Cell Biol 2005; 7(12): 1261-6.
  34. Rehwinkel J, Behm-Ansmant I, Gatfield D, Izaurralde E. A crucial role for GW182 and the DCP1:DCP2 decapping complex in miRNA-mediated gene silencing. RNA 2005; 11(11): 1640-7.
  35. Pillai RS, Bhattacharyya SN, Artus CG, Zoller T, Cougot N, Basyuk E, et al. Inhibition of translational initiation by Let-7 MicroRNA in human cells. Science 2005; 309(5740): 1573-6.
  36. Mathonnet G, Fabian MR, Svitkin YV, Parsyan A, Huck L, Murata T, et al. MicroRNA inhibition of translation initiation in vitro by targeting the cap-binding complex eIF4F. Science 2007; 317(5845): 1764-7.
  37. Thermann R, Hentze MW. Drosophila miR2 induces pseudo-polysomes and inhibits translation initiation. Nature 2007; 447(7146): 875-8.
  38. Wakiyama M, Takimoto K, Ohara O, Yokoyama S. Let-7 microRNA-mediated mRNA deadenylation and translational repression in a mammalian cell-free system. Genes Dev 2007; 21(15): 1857-62.
  39. Olsen PH, Ambros V. The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev Biol 1999; 216(2): 671-80.
  40. Seggerson K, Tang L, Moss EG. Two genetic circuits repress the Caenorhabditis elegans heterochronic gene lin-28 after translation initiation. Dev Biol 2002; 243(2): 215-25.
  41. Maroney PA, Yu Y, Fisher J, Nilsen TW. Evidence that microRNAs are associated with translating messenger RNAs in human cells. Nat Struct Mol Biol 2006; 13(12): 1102-7.
  42. Nottrott S, Simard MJ, Richter JD. Human let-7a miRNA blocks protein production on actively translating polyribosomes. Nat Struct Mol Biol 2006; 13(12): 1108-14.
  43. Petersen CP, Bordeleau ME, Pelletier J, Sharp PA. Short RNAs repress translation after initiation in mammalian cells. Mol Cell 2006; 21(4): 533-42.
  44. Zamore PD, Tuschl T, Sharp PA, Bartel DP. RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 2000; 101(1): 25-33.
  45. Llave C, Xie Z, Kasschau KD, Carrington JC. Cleavage of Scarecrow-like mRNA targets directed by a class of Arabidopsis miRNA. Science 2002; 297(5589): 2053-6.
  46. Yekta S, Shih IH, Bartel DP. MicroRNA-directed cleavage of HOXB8 mRNA. Science 2004; 304(5670): 594-6.
  47. Orban TI, Izaurralde E. Decay of mRNAs targeted by RISC requires XRN1, the Ski complex, and the exosome. RNA 2005; 11(4): 459-69.
  48. Wu L, Fan J, Belasco JG. MicroRNAs direct rapid deadenylation of mRNA. Proc Natl Acad Sci U S A 2006; 103(11): 4034-9.
  49. Giraldez AJ, Mishima Y, Rihel J, Grocock RJ, van Dongen S, Inoue K, et al. Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science 2006; 312(5770): 75-9.
  50. Eulalio A, Rehwinkel J, Stricker M, Huntzinger E, Yang SF, Doerks T, et al. Target-specific requirements for enhancers of decapping in miRNA-mediated gene silencing. Genes Dev 2007; 21(20): 2558-70.
  51. Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A 2006; 103(33): 12481-6.
  52. Perry MM, Moschos SA, Williams AE, Shepherd NJ, Larner-Svensson HM, Lindsay MA. Rapid changes in microRNA-146a expression negatively regulate the IL-1beta-induced inflammatory response in human lung alveolar epithelial cells. J Immunol 2008; 180(8): 5689-98.
  53. Tili E, Michaille JJ, Cimino A, Costinean S, Dumitru CD, Adair B, et al. Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol 2007; 179(8): 5082-9.
  54. O'Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D. MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci U S A 2007; 104(5): 1604-9.
  55. Haasch D, Chen YW, Reilly RM, Chiou XG, Koterski S, Smith ML, et al. T cell activation induces a noncoding RNA transcript sensitive to inhibition by immunosuppressant drugs and encoded by the proto-oncogene, BIC. Cell Immunol 2002; 217(1-2): 78-86.
  56. van den Berg A, Kroesen BJ, Kooistra K, de JD, Briggs J, Blokzijl T, et al. High expression of B-cell receptor inducible gene BIC in all subtypes of Hodgkin lymphoma. Genes Chromosomes Cancer 2003; 37(1): 20-8.
  57. Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR, et al. Requirement of bic/microRNA-155 for normal immune function. Science 2007; 316(5824): 608-11.
  58. Thai TH, Calado DP, Casola S, Ansel KM, Xiao C, Xue Y, et al. Regulation of the germinal center response by microRNA-155. Science 2007; 316(5824): 604-8.
  59. Vigorito E, Perks KL, Abreu-Goodger C, Bunting S, Xiang Z, Kohlhaas S, et al. microRNA-155 regulates the generation of immunoglobulin class-switched plasma cells. Immunity 2007; 27(6): 847-59.
  60. Chen CZ, Li L, Lodish HF, Bartel DP. MicroRNAs modulate hematopoietic lineage differentiation. Science 2004; 303(5654): 83-6.
  61. Li QJ, Chau J, Ebert PJ, Sylvester G, Min H, Liu G, et al. miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell 2007; 129(1): 147-61.
  62. de Yebenes VG, Belver L, Pisano DG, Gonzalez S, Villasante A, Croce C, et al. miR-181b negatively regulates activation-induced cytidine deaminase in B cells. J Exp Med 2008; 205(10): 2199-206.
  63. Fazi F, Rosa A, Fatica A, Gelmetti V, De Marchis ML, Nervi C, et al. A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis. Cell 2005; 123(5): 819-31.
  64. Fukao T, Fukuda Y, Kiga K, Sharif J, Hino K, Enomoto Y, et al. An evolutionarily conserved mechanism for microRNA-223 expression revealed by microRNA gene profiling. Cell 2007; 129(3): 617-31.
  65. Zhou B, Wang S, Mayr C, Bartel DP, Lodish HF. miR-150, a microRNA expressed in mature B and T cells, blocks early B cell development when expressed prematurely. Proc Natl Acad Sci U S A 2007; 104(17): 7080-5.
  66. Xiao C, Calado DP, Galler G, Thai TH, Patterson HC, Wang J, et al. MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb. Cell 2007; 131(1): 146-59.
  67. Yu D, Tan AH, Hu X, Athanasopoulos V, Simpson N, Silva DG, et al. Roquin represses autoimmunity by limiting inducible T-cell co-stimulator messenger RNA. Nature 2007; 450(7167): 299-303.
  68. Liston A, Lu LF, O'Carroll D, Tarakhovsky A, Rudensky AY. Dicer-dependent microRNA pathway safeguards regulatory T cell function. J Exp Med 2008; 205(9): 1993-2004.
  69. Zhou X, Jeker LT, Fife BT, Zhu S, Anderson MS, McManus MT, et al. Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity. J Exp Med 2008; 205(9): 1983-91.
  70. Nakasa T, Miyaki S, Okubo A, Hashimoto M, Nishida K, Ochi M, et al. Expression of microRNA-146 in rheumatoid arthritis synovial tissue. Arthritis Rheum 2008; 58(5): 1284-92.
  71. Pauley KM, Satoh M, Chan AL, Bubb MR, Reeves WH, Chan EK. Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthritis Res Ther 2008; 10(4): R101.
  72. Stanczyk J, Pedrioli DM, Brentano F, Sanchez-Pernaute O, Kolling C, Gay RE, et al. Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum 2008; 58(4): 1001-9.
  73. Dai Y, Huang YS, Tang M, Lv TY, Hu CX, Tan YH, et al. Microarray analysis of microRNA expression in peripheral blood cells of systemic lupus erythematosus patients. Lupus 2007; 16(12): 939-46.
  74. Dai Y, Sui W, Lan H, Yan Q, Huang H, Huang Y. Comprehensive analysis of microRNA expression patterns in renal biopsies of lupus nephritis patients. Rheumatol Int 2009; 29(7): 749-54.
  75. Kosik KS. The neuronal microRNA system. Nat Rev Neurosci 2006; 7(12): 911-20.
  76. Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 2007; 129(7): 1401-14.
  77. Berezikov E, Thuemmler F, van Laake LW, Kondova I, Bontrop R, Cuppen E, et al. Diversity of microRNAs in human and chimpanzee brain. Nat Genet 2006; 38(12): 1375-7.
  78. Giraldez AJ, Cinalli RM, Glasner ME, Enright AJ, Thomson JM, Baskerville S, et al. MicroRNAs regulate brain morphogenesis in zebrafish. Science 2005; 308(5723): 833-8.
  79. Bernstein E, Kim SY, Carmell MA, Murchison EP, Alcorn H, Li MZ, et al. Dicer is essential for mouse development. Nat Genet 2003; 35(3): 215-7.
  80. Kim J, Inoue K, Ishii J, Vanti WB, Voronov SV, Murchison E, et al. A MicroRNA feedback circuit in midbrain dopamine neurons. Science 2007; 317(5842): 1220-4.
  81. Schaefer A, O'Carroll D, Tan CL, Hillman D, Sugimori M, Llinas R, et al. Cerebellar neurodegeneration in the absence of microRNAs. J Exp Med 2007; 204(7): 1553-8.
  82. Davis TH, Cuellar TL, Koch SM, Barker AJ, Harfe BD, McManus MT, et al. Conditional loss of Dicer disrupts cellular and tissue morphogenesis in the cortex and hippocampus. J Neurosci 2008; 28(17): 4322-30.
  83. Damiani D, Alexander JJ, O'Rourke JR, McManus M, Jadhav AP, Cepko CL, et al. Dicer inactivation leads to progressive functional and structural degeneration of the mouse retina. J Neurosci 2008; 28(19): 4878-87.
  84. Schratt GM, Tuebing F, Nigh EA, Kane CG, Sabatini ME, Kiebler M, et al. A brain-specific microRNA regulates dendritic spine development. Nature 2006; 439(7074): 283-9.
  85. Visvanathan J, Lee S, Lee B, Lee JW, Lee SK. The microRNA miR-124 antagonizes the anti-neural REST/SCP1 pathway during embryonic CNS development. Genes Dev 2007; 21(7): 744-9.
  86. Makeyev EV, Zhang J, Carrasco MA, Maniatis T. The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol Cell 2007; 27(3): 435-48.
Journal of Isfahan Medical School
Volume 32, Issue 296 - Serial Number 296
July and August 2014
Pages 1259-1268

Files

History

  • Receive Date: 22 April 2014
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics