Review Article | Volume: 5, Issue: 2, March-April, 2017

Recent developments in understanding the mechanism and functions of microRNAs

Suhail Muzaffar Karishma Bisht   

Open Access   

Published:  Mar 20, 2017

DOI: 10.7324/JABB.2017.50201

Based on their mechanism of action and biological function, several classes of small RNAs have come into the limelight in the last two decades. These small RNA molecules generally belong to three main categories: short interfering RNAs (siRNAs), microRNAs (miRNAs), and piwi-interacting RNAs (piRNAs). miRNAs and siRNAs are distinguished primarily because miRNAs are endogenous in nature and are expressed by an organism's own genome, whereas siRNAs are exogenous in origin and derived mainly from the viruses and transposons. The first miRNA, lin-4, was discovered in 1993 as an endogenous regulator of genes that control developmental timing in Caenorhabditis elegans. miRNAs are coded by both plant and animal genomes and their transcription is typically performed by RNA polymerase II. MicroRNAs repress the expression of many genes by accelerating messenger RNA degradation as well as translational inhibition, thereby reducing the level of protein. Due to their involvement in various diseases like cancer, miRNAs have been a focus of scientific research for their potential as a new generation of drugs. The recent findings in miRNA research have been summarized in this review to add new dimensions to miRNA mechanism and functions.

Keyword:     MicroRNA MicroRNA biogenesis Functions of microRNAs.


Muzaffar S, Bisht K. Recent developments in understanding the mechanism and functions of microRNAs. J App Biol Biotech. 2017; 5 (02): 001-007. DOI: 10.7324/JABB.2017.50201

Copyright: Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike license.

HTML Full Text

1. RW Carthew, EJ Sontheimer. Origins and mechanisms of miRNAs and siRNAs. Cell. 2009; 136: 642-655

2. DP Bartel. MicroRNAs: genomics, biogenesis, mechanism, and function. cell. 2004; 116: 281-297

3. MI Almeida, RM Reis, GA Calin. MicroRNA history: discovery, recent applications, and next frontiers. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 2011; 717: 1-8

4. A Fire, S Xu, MK Montgomery, SA Kostas, SE Driver, CC Mello. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998; 391: 806-811

5. H Tabara, M Sarkissian, WG Kelly, J Fleenor, A Grishok, L Timmons, A Fire, CC Mello. The rde-1 gene, RNA interference, and transposon silencing in C. elegans. Cell. 1999; 99: 123-132

6. PD Zamore, T Tuschl, PA Sharp, DP Bartel. RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell. 2000; 101: 25-33

7. SM Hammond, E Bernstein, D Beach, GJ Hannon. An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature. 2000; 404: 293-296

8. E Bernstein, AA Caudy, SM Hammond, GJ Hannon. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 2001; 409: 363-366

9. RF Ketting, SE Fischer, E Bernstein, T Sijen, GJ Hannon, RH Plasterk. Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes & development. 2001; 15: 2654-2659

10. A Grishok, AE Pasquinelli, D Conte, N Li, S Parrish, I Ha, DL Baillie, A Fire, G Ruvkun, CC Mello. Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell. 2001; 106: 23-34

11. RC Lee, RL Feinbaum, V Ambros. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993; 75: 843-854

12. BJ Reinhart, FJ Slack, M Basson, AE Pasquinelli, JC Bettinger, AE Rougvie, HR Horvitz, G Ruvkun. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature. 2000; 403: 901-906

13. M Lagos-Quintana, R Rauhut, J Meyer, A Borkhardt, T Tuschl. New microRNAs from mouse and human. RNA. 2003; 9: 175-179

14. Y Lee, M Kim, J Han, KH Yeom, S Lee, SH Baek, VN Kim. MicroRNA genes are transcribed by RNA polymerase II. The EMBO journal. 2004; 23: 4051-4060

15. GM Borchert, W Lanier, BL Davidson. RNA polymerase III transcribes human microRNAs. Nature structural & molecular biology. 2006; 13: 1097-1101

16. Y Lee, K Jeon, JT Lee, S Kim, VN Kim. MicroRNA maturation: stepwise processing and subcellular localization. The EMBO journal. 2002; 21: 4663-4670

17. E Lund, S Güttinger, A Calado, JE Dahlberg, U Kutay. Nuclear export of microRNA precursors. Science. 2004; 303: 95-98

18. G Hutvágner, J McLachlan, AE Pasquinelli, É Bálint, T Tuschl, PD Zamore. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science. 2001; 293: 834-838

19. SM Hammond. Dicing and slicing. FEBS letters. 2005; 579: 5822-5829

20. S Matsuda, Y Ichigotani, T Okuda, T Irimura, S Nakatsugawa, M Hamaguchi. Molecular cloning and characterization of a novel human gene (HERNA) which encodes a putative RNA-helicase. Biochimica et Biophysica Acta (BBA)-Gene Structure and Expression. 2000; 1490: 163-169

21. IJ MacRae, K Zhou, F Li, A Repic, AN Brooks, WZ Cande, PD Adams, JA Doudna. Structural basis for double-stranded RNA processing by Dicer. Science. 2006; 311: 195-198

22. W Filipowicz, SN Bhattacharyya, N Sonenberg. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nature Reviews Genetics. 2008; 9: 102-114

23. RI Gregory, TP Chendrimada, N Cooch, R Shiekhattar. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell. 2005; 123: 631-640

24. J-B Ma, K Ye, DJ Patel. Structural basis for overhang-specific small interfering RNA recognition by the PAZ domain. Nature. 2004; 429: 318-322

25. MA Carmell, Z Xuan, MQ Zhang, GJ Hannon. The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis. Genes & development. 2002; 16: 2733-2742

26. G Meister, M Landthaler, A Patkaniowska, Y Dorsett, G Teng, T Tuschl. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Molecular cell. 2004; 15: 185-197

27. V Ambros. The functions of animal microRNAs. Nature. 2004; 431: 350-355

28. L Wu, J Fan, JG Belasco. MicroRNAs direct rapid deadenylation of mRNA. Proceedings of the National Academy of Sciences of the United States of America. 2006; 103: 4034-4039

29. M Brengues, D Teixeira, R Parker. Movement of eukaryotic mRNAs between polysomes and cytoplasmic processing bodies. Science. 2005; 310: 486-489

30. J Liu, FV Rivas, J Wohlschlegel, JR Yates, R Parker, GJ Hannon. A role for the P-body component GW182 in microRNA function. Nature cell biology. 2005; 7: 1261-1266

31. A Jakymiw, S Lian, T Eystathioy, S Li, M Satoh, JC Hamel, MJ Fritzler, EK Chan. Disruption of GW bodies impairs mammalian RNA interference. Nature cell biology. 2005; 7: 1267-1274

32. H Guo, NT Ingolia, JS Weissman, DP Bartel. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010; 466: 835-840

33. S Vasudevan, Y Tong, JA Steitz. Switching from repression to activation: microRNAs can up-regulate translation. Science. 2007; 318: 1931-1934

34. M KatoFJ Slack. microRNAs: small molecules with big roles–C. elegans to human cancer. Biology of the Cell. 2008; 100: 71-81

35. R Nolo, CM Morrison, C Tao, X Zhang, G Halder. The bantam microRNA is a target of the hippo tumor-suppressor pathway. Current Biology. 2006; 16: 1895-1904

36. Y Zhao, E Samal, D Srivastava. Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature. 2005; 436: 214-220

37. MN Poy, L Eliasson, J Krutzfeldt, S Kuwajima, X Ma, PE MacDonald, S Pfeffer, T Tuschl, N Rajewsky, P Rorsman. A pancreatic islet-specific microRNA regulates insulin secretion. Nature. 2004; 432: 226-230

38. H Rupani, T Sanchez-Elsner, P Howarth. MicroRNAs and respiratory diseases. European Respiratory Journal. 2013; 41: 695-705

39. S Maltby, M Plank, HL Tay, A Collison, PS Foster. Targeting MicroRNA function in respiratory diseases: mini-review. Frontiers in physiology. 2016; 7:

40. F Sonneville, M Ruffin, L Guillot, N Rousselet, P Le Rouzic, H Corvol, O Tabary. New insights about miRNAs in cystic fibrosis. The American journal of pathology. 2015; 185: 897-908

41. R SunkarJ-K Zhu. Novel and stress-regulated microRNAs and other small RNAs from Arabidopsis. The Plant Cell. 2004; 16: 2001-2019

42. MT Juarez, JS Kui, J Thomas, BA Heller, MC Timmermans. microRNA-mediated repression of rolled leaf1 specifies maize leaf polarity. Nature. 2004; 428: 84-88

43. MJ AukermanH Sakai. Regulation of flowering time and floral organ identity by a microRNA and its APETALA2-like target genes. The Plant Cell. 2003; 15: 2730-2741

44. P Achard, A Herr, DC Baulcombe, NP Harberd. Modulation of floral development by a gibberellin-regulated microRNA. Development. 2004; 131: 3357-3365

45. R Schwab, JF Palatnik, M Riester, C Schommer, M Schmid, D Weigel. Specific effects of microRNAs on the plant transcriptome. Developmental cell. 2005; 8: 517-527

46. AA MillarF Gubler. The Arabidopsis GAMYB-like genes, MYB33 and MYB65, are microRNA-regulated genes that redundantly facilitate anther development. The Plant Cell. 2005; 17: 705-721

47. Y-C Zhang, Y Yu, C-Y Wang, Z-Y Li, Q Liu, J Xu, J-Y Liao, X-J Wang, L-H Qu, F Chen. Overexpression of microRNA OsmiR397 improves rice yield by increasing grain size and promoting panicle branching. Nature biotechnology. 2013; 31: 848-852

48. C LiB Zhang. MicroRNAs in control of plant development. Journal of Cellular Physiology. 2016; 231: 303-313

49. Á Mencía, S Modamio-Høybjør, N Redshaw, M Morín, F Mayo-Merino, L Olavarrieta, LA Aguirre, I del Castillo, KP Steel, T Dalmay. Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss. Nature genetics. 2009; 41: 609-613

50. K MusilovaM Mraz. MicroRNAs in B-cell lymphomas: how a complex biology gets more complex. Leukemia. 2015; 29: 1004-1017

51. T Thum, P Galuppo, C Wolf, J Fiedler, S Kneitz, LW van Laake, PA Doevendans, CL Mummery, J Borlak, A Haverich. MicroRNAs in the human heart a clue to fetal gene reprogramming in heart failure. Circulation. 2007; 116: 258-267

52. W Insull. The pathology of atherosclerosis: plaque development and plaque responses to medical treatment. The American journal of medicine. 2009; 122: S3-S14

53. JM Romao, W Jin, MV Dodson, GJ Hausman, SS Moore. MicroRNA regulation in mammalian adipogenesis. Experimental Biology and Medicine. 2011; 236: 997-1004

54. L de Pontual, E Yao, P Callier, L Faivre, V Drouin, S Cariou, A Van Haeringen, D Geneviève, A Goldenberg, M Oufadem. Germline deletion of the miR-17 [sim] 92 cluster causes skeletal and growth defects in humans. Nature genetics. 2011; 43: 1026-1030

55. ND Amin, G Bai, JR Klug, D Bonanomi, MT Pankratz, WD Gifford, CA Hinckley, MJ Sternfeld, SP Driscoll, B Dominguez. Loss of motoneuron-specific microRNA-218 causes systemic neuromuscular failure. Science. 2015; 350: 1525-1529

56. G Schratt. microRNAs at the synapse. Nature Reviews Neuroscience. 2009; 10: 842-849

57. LG Hommers, K Domschke, J Deckert. Heterogeneity and individuality: microRNAs in mental disorders. Journal of Neural Transmission. 2015; 122: 79-97

58. J Brennecke, DR Hipfner, A Stark, RB Russell, SM Cohen. bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell. 2003; 113: 25-36

59. EC Lai, B Tam, GM Rubin. Pervasive regulation of Drosophila Notch target genes by GY-box-, Brd-box-, and K-box-class microRNAs. Genes & development. 2005; 19: 1067-1080

60. C-H Lecellier, P Dunoyer, K Arar, J Lehmann-Che, S Eyquem, C Himber, A Saïb, O Voinnet. A cellular microRNA mediates antiviral defense in human cells. Science. 2005; 308: 557-560

61. T-C Chang, D Yu, Y-S Lee, EA Wentzel, DE Arking, KM West, CV Dang, A Thomas-Tikhonenko, JT Mendell. Widespread microRNA repression by Myc contributes to tumorigenesis. Nature genetics. 2008; 40: 43-50

62. F Fazi, A Rosa, A Fatica, V Gelmetti, ML De Marchis, C Nervi, I Bozzoni. A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPα regulates human granulopoiesis. Cell. 2005; 123: 819-831

63. J-W Wang, R Schwab, B Czech, E Mica, D Weigel. Dual effects of miR156-targeted SPL genes and CYP78A5/KLUH on plastochron length and organ size in Arabidopsis thaliana. The Plant Cell. 2008; 20: 1231-1243

64. AC Mallory, DV Dugas, DP Bartel, B Bartel. MicroRNA regulation of NAC-domain targets is required for proper formation and separation of adjacent embryonic, vegetative, and floral organs. Current Biology. 2004; 14: 1035-1046

65. H-S Guo, Q Xie, J-F Fei, N-H Chua. MicroRNA directs mRNA cleavage of the transcription factor NAC1 to downregulate auxin signals for Arabidopsis lateral root development. The Plant Cell. 2005; 17: 1376-1386

66. CX Qiu, FL Xie, YY Zhu, K Guo, SQ Huang, L Nie, ZM Yang. Computational identification of microRNAs and their targets in Gossypium hirsutum expressed sequence tags. Gene. 2007; 395: 49-61

67. JF Palatnik, E Allen, X Wu, C Schommer, R Schwab, JC Carrington, D Weigel. Control of leaf morphogenesis by microRNAs. Nature. 2003; 425: 257-263

68. B Zhang, X Pan, TA Anderson. Identification of 188 conserved maize microRNAs and their targets. Febs Letters. 2006; 580: 3753-3762

69. MW Jones-RhoadesDP Bartel. Computational identification of plant microRNAs and their targets, including a stress-induced miRNA. Molecular cell. 2004; 14: 787-799

70. E Allen, Z Xie, AM Gustafson, JC Carrington. microRNA-directed phasing during trans-acting siRNA biogenesis in plants. Cell. 2005; 121: 207-221

Article Metrics
114 Views 54 Downloads 168 Total



Related Search

By author names

Similar Articles