Advertisement

Molecular Genetics and Genomics

, Volume 284, Issue 2, pp 95–103 | Cite as

Many ways to generate microRNA-like small RNAs: non-canonical pathways for microRNA production

  • Keita Miyoshi
  • Tomohiro Miyoshi
  • Haruhiko Siomi
Review

Abstract

MicroRNAs (miRNAs) are an abundant class of small non-coding RNAs that collectively regulate the expression of a large number of mRNAs by either promoting destabilization or repressing translation, or both. Therefore, they play a major role in shaping the transcriptomes and proteomes of eukaryotic organisms. Typically, animal miRNAs are produced from long primary transcripts with one or more of hairpin structures by two sequential processing reactions: one by Drosha in the nucleus and the other by Dicer in the cytoplasm. However, deviations from this paradigm have been observed: subclasses of miRNAs, which only partially meet the classical definition of a miRNA, are derived by alternative biogenesis pathways, thereby providing an additional level of complexity to miRNA-dependent regulation of gene expression.

Keywords

miRNA Drosha Dicer Argonaute snoRNA tRNA 

Notes

Acknowledgments

The authors would like to thank the members of the Siomi Laboratory for discussions. This work was supported by MEXT grants to H.S and K.M, and a Keio University Grant-in-Aid for Encouragement of Young Medical Scientists to K.M.

References

  1. Altman S (2000) The road to RNase P. Nat Struct Biol 7:827–828CrossRefPubMedGoogle Scholar
  2. Azuma-Mukai A, Oguri H, Mituyama T, Qian ZR, Asai K, Siomi H, Siomi MC (2008) Characterization of endogenous human Argonautes and their miRNA partners in RNA silencing. Proc Natl Acad Sci USA 105:7964–7969CrossRefPubMedGoogle Scholar
  3. Babiarz JE, Ruby JG, Wang Y, Bartel DP, Blelloch R (2008) Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs. Genes Dev 22:2773–2785CrossRefPubMedGoogle Scholar
  4. Baek D, Villén J, Shin C, Camargo FD, Gygi SP, Bartel DP (2008) The impact of microRNAs on protein output. Nature 455:64–71CrossRefPubMedGoogle Scholar
  5. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233CrossRefPubMedGoogle Scholar
  6. Berezikov E, van Tetering G, Verheul M, van de Belt J, van Laake L, Vos J, Verloop R, van de Wetering M, Guryev V, Takada S, van Zonneveld AJ, Mano H, Plasterk R, Cuppen E (2006) Many novel mammalian microRNA candidates identified by extensive cloning and RAKE analysis. Genome Res 16:1289–1298CrossRefPubMedGoogle Scholar
  7. Berezikov E, Chung WJ, Willis J, Cuppen E, Lai EC (2007) Mammalian mirtron genes. Mol Cell 28:328–336CrossRefPubMedGoogle Scholar
  8. Bhattacharyya SN, Habermacher R, Martine U, Closs EI, Filipowicz W (2006) Relief of microRNA-mediated translational repression in human cells subjected to stress. Cell 125:1111–1124CrossRefPubMedGoogle Scholar
  9. Bogerd HP, Karnowski HW, Cai X, Shin J, Pohlers M, Cullen BR (2010) A mammalian herpesvirus uses noncanonical expression and processing mechanisms to generate viral microRNAs. Mol Cell 37:135–142CrossRefPubMedGoogle Scholar
  10. Brodersen P, Voinnet O (2009) Revisiting the principles of microRNA target recognition and mode of action. Nat Rev Mol Cell Biol 10:141–148CrossRefPubMedGoogle Scholar
  11. Bushati N, Cohen SM (2007) microRNA functions. Annu Rev Cell Dev Biol 23:175–205CrossRefPubMedGoogle Scholar
  12. Cai X, Hagedorn CH, Cullen BR (2004) Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 10:1957–1966CrossRefPubMedGoogle Scholar
  13. Carthew RW, Sontheimer EJ (2009) Origins and Mechanisms of miRNAs and siRNAs. Cell 136:642–655CrossRefPubMedGoogle Scholar
  14. Chang TC, Mendell JT (2007) microRNAs in vertebrate physiology and human disease. Annu Rev Genomics Hum Genet 8:215–239CrossRefPubMedGoogle Scholar
  15. Cheloufi S, Dos Santos CO, Chong MM, Hannon GJ (2010) A dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature 465:584–589CrossRefPubMedGoogle Scholar
  16. Chen X (2009) Small RNAs and their roles in plant development. Annu Rev Cell Dev Biol 25:21–44CrossRefPubMedGoogle Scholar
  17. Chendrimada TP, Gregory RI, Kumaraswamy E, Norman J, Cooch N, Nishikura K, Shiekhattar R (2005) TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature 436:740–744CrossRefPubMedGoogle Scholar
  18. Cifuentes D, Xue H, Taylor DW, Patnode H, Mishima Y, Cheloufi S, Ma E, Mane S, Hannon GJ, Lawson N, Wolfe S, Giraldez AJ (2010) A novel miRNA processing pathway independent of Dicer requires Argonaute2 catalytic activity. Science 328:1694–1698CrossRefPubMedGoogle Scholar
  19. Cole C, Sobala A, Lu C, Thatcher SR, Bowman A, Brown JW, Green PJ, Barton GJ, Hutvagner G (2009) Filtering of deep sequencing data reveals the existence of abundant Dicer-dependent small RNAs derived from tRNAs. RNA 15:2147–2160CrossRefPubMedGoogle Scholar
  20. Cordes KR, Sheehy NT, White MP, Berry EC, Morton SU, Muth AN, Lee TH, Miano JM, Ivey KN, Srivastava D (2009) miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature 460:705–710PubMedGoogle Scholar
  21. Czech B, Zhou R, Erlich Y, Brennecke J, Binari R, Villalta C, Gordon A, Perrimon N, Hannon GJ (2009) Hierarchical rules for Argonaute loading in Drosophila. Mol Cell 36:445–456CrossRefPubMedGoogle Scholar
  22. Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ (2004) Processing of primary microRNAs by the Microprocessor complex. Nature 432:231–235CrossRefPubMedGoogle Scholar
  23. Elbashir SM, Martinez J, Patkaniowska A, Lendeckel W, Tuschl T (2001) Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. EMBO J 20:6877–6888CrossRefPubMedGoogle Scholar
  24. Ender C, Krek A, Friedländer MR, Beitzinger M, Weinmann L, Chen W, Pfeffer S, Rajewsky N, Meister G (2008) A human snoRNA with microRNA-like functions. Mol Cell 32:519–528CrossRefPubMedGoogle Scholar
  25. Filipowicz W, Bhattacharyya SN, Sonenberg N (2008) Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 9:102–114CrossRefPubMedGoogle Scholar
  26. Förstemann K, Tomari Y, Du T, Vagin VV, Denli AM, Bratu DP, Klattenhoff C, Theurkauf WE, Zamore PD (2005) Normal microRNA maturation and germ-line stem cell maintenance requires Loquacious, a double-stranded RNA-binding domain protein. PLoS Biol 3:e236CrossRefPubMedGoogle Scholar
  27. Friedman RC, Farh KK, Burge CB, Bartel DP (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19:92–105CrossRefPubMedGoogle Scholar
  28. Garzon R, Calin GA, Croce CM (2009) MicroRNAs in Cancer. Annu Rev Med 60:167–179CrossRefPubMedGoogle Scholar
  29. Ghildiyal M, Xu J, Seitz H, Weng Z, Zamore PD (2010) Sorting of Drosophila small silencing RNAs partitions microRNA* strands into the RNA interference pathway. RNA 16:43–56CrossRefPubMedGoogle Scholar
  30. Gregory RI, Yan KP, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, Shiekhattar R (2004) The Microprocessor complex mediates the genesis of microRNAs. Nature 432:235–240CrossRefPubMedGoogle Scholar
  31. Grimson A, Srivastava M, Fahey B, Woodcroft BJ, Chiang HR, King N, Degnan BM, Rokhsar DS, Bartel DP (2008) Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals. Nature 455:1193–1197CrossRefPubMedGoogle Scholar
  32. Gu S, Jin L, Zhang F, Sarnow P, Kay MA (2009) Biological basis for restriction of microRNA targets to the 3′ untranslated region in mammalian mRNAs. Nat Struct Mol Biol 16:144–150CrossRefPubMedGoogle Scholar
  33. Han J, Lee Y, Yeom KH, Nam JW, Heo I, Rhee JK, Sohn SY, Cho Y, Zhang BT, Kim VN (2006) Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell 125:887–901CrossRefPubMedGoogle Scholar
  34. Hartig JV, Esslinger S, Böttcher R, Saito K, Förstemann K (2009) Endo-siRNAs depend on a new isoform of loquacious and target artificially introduced, high-copy sequences. EMBO J 28:2932–2944CrossRefPubMedGoogle Scholar
  35. Haussecker D, Huang Y, Lau A, Parameswaran P, Fire AZ, Kay MA (2010) Human tRNA-derived small RNAs in the global regulation of RNA silencing. RNA 16:673–695CrossRefPubMedGoogle Scholar
  36. Hu HY, Yan Z, Xu Y, Hu H, Menzel C, Zhou YH, Chen W, Khaitovich P (2009) Sequence features associated with microRNA strand selection in humans and flies. BMC Genomics 10:413CrossRefPubMedGoogle Scholar
  37. Hüttenhofer A, Schattner P (2006) The principles of guiding by RNA: chimeric RNA-protein enzymes. Nat Rev Genet 7:475–482CrossRefPubMedGoogle Scholar
  38. Hutvagner G, Simard MJ (2008) Argonaute proteins: key players in RNA silencing. Nat Rev Mol Cell Biol 9:22–32CrossRefPubMedGoogle Scholar
  39. Jiang F, Ye X, Liu X, Fincher L, McKearin D, Liu Q (2005) Dicer-1 and R3D1-L catalyze microRNA maturation in Drosophila. Genes Dev 19:1674–1679CrossRefPubMedGoogle Scholar
  40. Kawaji H, Nakamura M, Takahashi Y, Sandelin A, Katayama S, Fukuda S, Daub CO, Kai C, Kawai J, Yasuda J, Carninci P, Hayashizaki Y (2008) Hidden layers of human small RNAs. BMC Genomics 9:157CrossRefPubMedGoogle Scholar
  41. Khvorova A, Reynolds A, Jayasena SD (2003) Functional siRNAs and miRNAs exhibit strand bias. Cell 115:209–216CrossRefPubMedGoogle Scholar
  42. Kim YK, Kim VN (2007) Processing of intronic microRNAs. EMBO J 26:775–783CrossRefPubMedGoogle Scholar
  43. Kim VN, Han J, Siomi MC (2009) Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 10:126–139CrossRefPubMedGoogle Scholar
  44. Lee Y, Hur I, Park SY, Kim YK, Suh MR, Kim VN (2006) The role of PACT in the RNA silencing pathway. EMBO J 25:522–532CrossRefPubMedGoogle Scholar
  45. Lee YS, Shibata Y, Malhotra A, Dutta A (2009) A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes Dev 23:2639–2649CrossRefPubMedGoogle Scholar
  46. Lim LP, Burge CB (2001) A computational analysis of sequence features involved in recognition of short introns. Proc Natl Acad Sci USA 98:11193–11198CrossRefPubMedGoogle Scholar
  47. Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS, Johnson JM (2005) Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433:769–773CrossRefPubMedGoogle Scholar
  48. Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM, Song JJ, Hammond SM, Joshua-Tor L, Hannon GJ (2004) Argonaute2 is the catalytic engine of mammalian RNAi. Science 305:1437–1441CrossRefPubMedGoogle Scholar
  49. Lund E, Dahlberg JE (1998) Proofreading and aminoacylation of tRNAs before export from the nucleus. Science 282:2082–2085CrossRefPubMedGoogle Scholar
  50. Ma JB, Yuan YR, Meister G, Pei Y, Tuschl T, Patel DJ (2005) Structural basis for 5′-end-specific recognition of guide RNA by the A. fulgidus Piwi protein. Nature 434:666–670CrossRefPubMedGoogle Scholar
  51. Mardis ER (2008) The impact of next-generation sequencing technology on genetics. Trends Genet 24:133–141PubMedGoogle Scholar
  52. Matera AG, Terns RM, Terns MP (2007) Non-coding RNAs: lessons from the small nuclear and small nucleolar RNAs. Nat Rev Mol Cell Biol 8:209–220CrossRefPubMedGoogle Scholar
  53. Mayer M, Schiffer S, Marchfelder A (2000) tRNA 3′ processing in plants: nuclear and mitochondrial activities differ. Biochemistry 39:2096–2105CrossRefPubMedGoogle Scholar
  54. Meister G, Landthaler M, Patkaniowska A, Dorset Y, Teng G, Tuschl T (2004) Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell 15:185–197CrossRefPubMedGoogle Scholar
  55. Miyoshi K, Miyoshi T, Hartig JV, Siomi H, Siomi MC (2010) Molecular mechanisms that funnel RNA precursors into endogenous small-interfering RNA and microRNA biogenesis pathways in Drosophila. RNA 16:506–515CrossRefPubMedGoogle Scholar
  56. Okada C, Yamashita E, Lee SJ, Shibata S, Katahira J, Nakagawa A, Yoneda Y, Tsukihara T (2009) A high-resolution structure of the pre-microRNA nuclear export machinery. Science 326:1275–1279CrossRefPubMedGoogle Scholar
  57. Okamura K, Lai EC (2008) Endogenous small interfering RNAs in animals. Nat Rev Mol Cell Biol 9:673–678CrossRefPubMedGoogle Scholar
  58. Okamura K, Hagen JW, Duan H, Tyler DM, Lai EC (2007) The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila. Cell 130:89–100CrossRefPubMedGoogle Scholar
  59. Okamura K, Phillips MD, Tyler DM, Duan H, Chou YT, Lai EC (2008) The regulatory activity of microRNA* species has substantial influence on microRNA and 3′ UTR evolution. Nat Struct Mol Biol 15:354–363CrossRefPubMedGoogle Scholar
  60. Okamura K, Liu N, Lai EC (2009) Distinct mechanisms for microRNA strand selection by Drosophila Argonautes. Mol Cell 36:431–444CrossRefPubMedGoogle Scholar
  61. Parker JS (2010) How to slice: snapshots of Argonaute in action. Silence 1:3CrossRefPubMedGoogle Scholar
  62. Parker JS, Roe SM, Barford D (2005) Structural insights into mRNA recognition from a PIWI domain-siRNA guide complex. Nature 434:663–666CrossRefPubMedGoogle Scholar
  63. Pfeffer S, Zavolan M, Grässer FA, Chien M, Russo JJ, Ju J, John B, Enright AJ, Marks D, Sander C, Tuschl T (2004) Identification of virus-encoded microRNAs. Science 304:734–736CrossRefPubMedGoogle Scholar
  64. Pfeffer S, Sewer A, Lagos-Quintana M, Sheridan R, Sander C, Grässer FA, van Dyk LF, Ho CK, Shuman S, Chien M, Russo JJ, Ju J, Randall G, Lindenbach BD, Rice CM, Simon V, Ho DD, Zavolan M, Tuschl T (2005) Identification of microRNAs of the herpesvirus family. Nat Methods 2:269–276CrossRefPubMedGoogle Scholar
  65. Ruby JG, Jan CH, Bartel DP (2007) Intronic microRNA precursors that bypass Drosha processing. Nature 448:83–86CrossRefPubMedGoogle Scholar
  66. Saito K, Ishizuka A, Siomi H, Siomi MC (2005) Processing of pre-microRNAs by the Dicer-1-Loquacious complex in Drosophila cells. PLoS Biol 3:e235CrossRefPubMedGoogle Scholar
  67. Saraiya AA, Wang CC (2008) snoRNA, novel precursor of microRNA in Giardia lamblia. PLoS Pathog 4:e1000224CrossRefPubMedGoogle Scholar
  68. Schwarz DS, Hutvágner G, Du T, Xu Z, Aronin N, Zamore PD (2003) Asymmetry in the assembly of the RNAi enzyme complex. Cell 115:199–208CrossRefPubMedGoogle Scholar
  69. Schwarz DS, Tomari Y, Zamore PD (2004) The RNA-induced silencing complex is a Mg2+-dependent endonuclease. Curr Biol 14:787–791CrossRefPubMedGoogle Scholar
  70. Scott MS, Avolio F, Ono M, Lamond AI, Barton GJ (2009) Human miRNA precursors with box H/ACA snoRNA features. PLoS Comput Biol 5:e1000507CrossRefPubMedGoogle Scholar
  71. Seitz H, Ghildiyal M, Zamore PD (2008) Argonaute loading improves the 5′ precision of both MicroRNAs and their miRNA strands in flies. Curr Biol 18:147–151CrossRefPubMedGoogle Scholar
  72. Selbach M, Schwanhäusser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N (2008) Widespread changes in protein synthesis induced by microRNAs. Nature 455:58–63CrossRefPubMedGoogle Scholar
  73. Siomi H, Siomi MC (2009) On the road to reading the RNA-interference code. Nature 457:396–404CrossRefPubMedGoogle Scholar
  74. Siomi H, Siomi MC (2010) Posttranscriptional regulation of miRNA biogenesis in animals. Mol Cell 38:323–332CrossRefPubMedGoogle Scholar
  75. Song JJ, Smith SK, Hannon GJ, Joshua-Tor L (2004) Crystal structure of Argonaute and its implications for RISC slicer activity. Science 305:1434–1437CrossRefPubMedGoogle Scholar
  76. Taft RJ, Glazov EA, Lassmann T, Hayashizaki Y, Carninci P, Mattick JS (2009) Small RNAs derived from snoRNAs. RNA 15:1233–1240CrossRefPubMedGoogle Scholar
  77. Technau U (2008) Evolutionary biology: small regulatory RNAs pitch in. Nature 455:1184–1185CrossRefPubMedGoogle Scholar
  78. Tomari Y, Du T, Zamore PD (2007) Sorting of Drosophila small silencing RNAs. Cell 130:299–308CrossRefPubMedGoogle Scholar
  79. Vasudevan S, Tong Y, Steitz JA (2007) Switching from repression to activation: microRNAs can up-regulate translation. Science 318:1931–1934CrossRefPubMedGoogle Scholar
  80. Wang HW, Noland C, Siridechadilok B, Taylor DW, Ma E, Felderer K, Doudna JA, Nogales E (2009) Structural insights into RNA processing by the human RISC-loading complex. Nat Struct Mol Biol 16:1148–1153CrossRefPubMedGoogle Scholar
  81. Weiner AM (2005) E pluribus unum: 3′ end formation of polyadenylated mRNAs, histone mRNAs, and U snRNAs. Mol Cell 20:168–170CrossRefPubMedGoogle Scholar
  82. Yu J, Yang Z, Kibukawa M, Paddock M, Passey DA, Wong GK (2002) Minimal introns are not “junk”. Genome Res 12:1185–1189CrossRefPubMedGoogle Scholar
  83. Zhou R, Czech B, Brennecke J, Sachidanandam R, Wohlschlegel JA, Perrimon N, Hannon GJ (2009) Processing of Drosophila endo-siRNAs depends on a specific Loquacious isoform. RNA 15:1886–1895CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Keita Miyoshi
    • 1
  • Tomohiro Miyoshi
    • 1
  • Haruhiko Siomi
    • 1
  1. 1.Department of Molecular BiologyKeio University School of MedicineTokyoJapan

Personalised recommendations