Abstract

MicroRNAs (miRNAs) are short (~22 nucleotides) single-stranded RNA molecules that primarily function to negatively regulate gene expression at the post-transcriptional level. miRNAs have thus been implicated in the regulation of a wide variety of normal cell functions and pathophysiological conditions. The miRNA machinery consists of a series of protein complexes which act to: (1) cleave the precursor-miRNA hairpin from its primary transcript (i.e. DROSHA and DGCR8); (2) traffic the miRNA hairpin between nucleus and cytoplasm (i.e. XPO5); (3) remove the loop sequence of the hairpin by a second nucleolytic cleavage reaction (i.e. DICER1); (4) facilitate loading of the mature miRNA sequence into an Argonaute protein (typically AGO2) as part of the RNA-Induced Silencing Complex (RISC); (5) guide the loaded RISC complex to complementary, or semi-complementary, target transcripts and (6) facilitate gene silencing via one of several possible mechanisms.

Keywords

Argonaute AGO2 Dicer DICER1 Exportin-5 XPO5 Drosha microRNA DGCR8 

References

  1. 1.
    Filipowicz W, Jaskiewicz L, Kolb FA, Pillai RS. Post-transcriptional gene silencing by siRNAs and miRNAs. Curr Opin Struct Biol. 2005;15:331–41.CrossRefPubMedGoogle Scholar
  2. 2.
    Roberts TC, Wood MJA. Therapeutic targeting of non-coding RNAs. Essays Biochem. 2013; 54:127–45.CrossRefPubMedGoogle Scholar
  3. 3.
    Cacchiarelli D, Incitti T, Martone J, Cesana M, Cazzella V, Santini T, Sthandier O, Bozzoni I. miR-31 modulates dystrophin expression: new implications for Duchenne muscular dystrophy therapy. EMBO Rep. 2011;12:136–41.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Wang L, Zhou L, Jiang P, Lu L, Chen X, Lan H, Guttridge DC, Sun H, Wang H. Loss of miR-29 in myoblasts contributes to dystrophic muscle pathogenesis. Mol Ther. 2012;20:1222–33.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Roberts TC, Godfrey C, McClorey G, Vader P, Briggs D, Gardiner C, Aoki Y, Sargent I, Morgan JE, Wood MJA. Extracellular microRNAs are dynamic non-vesicular biomarkers of muscle turnover. Nucleic Acids Res. 2013;41:9500–13.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105:10513–8.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Gilad S, Meiri E, Yogev Y, et al. Serum microRNAs are promising novel biomarkers. PLoS One. 2008;3, e3148.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Lee Y, Kim M, Han J, Yeom K-H, Lee S, Baek SH, Kim VN. MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 2004;23:4051–60.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Cai X, Hagedorn CH, Cullen BR. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA. 2004;10:1957–66.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Kim Y-K, Kim VN. Processing of intronic microRNAs. EMBO J. 2007;26:775–83.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science. 2001;294:853–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Mogilyansky E, Rigoutsos I. The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease. Cell Death Differ. 2013;20:1603–14.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Lee Y, Jeon K, Lee J-T, Kim S, Kim VN. MicroRNA maturation: stepwise processing and subcellular localization. EMBO J. 2002;21:4663–70.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    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; 216:671–80.CrossRefPubMedGoogle Scholar
  15. 15.
    Doench JG, Sharp PA. Specificity of microRNA target selection in translational repression. Genes Dev. 2004;18:504–11.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Ohler U, Yekta S, Lim LP, Bartel DP, Burge CB. Patterns of flanking sequence conservation and a characteristic upstream motif for microRNA gene identification. RNA. 2004;10:1309–22.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Guo H, Ingolia NT, Weissman JS, Bartel DP. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010;466:835–40.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell. 2005;123:631–40.CrossRefPubMedGoogle Scholar
  19. 19.
    Roberts TC. The microRNA biology of the mammalian nucleus. Mol Ther Nucleic Acids. 2014;3:e188Google Scholar
  20. 20.
    Roberts TC, Wood MJ. Non-canonical microRNA biogenesis and function. In: Arbuthnot P, Weinberg M, editors. Applied RNAi: from fundamental research to therapeutic applications. Norfolk: Caister Academic Press; 2014. p. 19–42.Google Scholar
  21. 21.
    Gregory RI, Yan K-P, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, Shiekhattar R. The Microprocessor complex mediates the genesis of microRNAs. Nature. 2004;432:235–40.CrossRefPubMedGoogle Scholar
  22. 22.
    Wu H, Xu H, Miraglia LJ, Crooke ST. Human RNase III is a 160-kDa protein involved in preribosomal RNA processing. J Biol Chem. 2000;275:36957–65.CrossRefPubMedGoogle Scholar
  23. 23.
    Lee Y, Ahn C, Han J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003;425:415–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Dalzell JJ, Warnock ND, Stevenson MA, Mousley A, Fleming CC, Maule AG. Short interfering RNA-mediated knockdown of drosha and pasha in undifferentiated Meloidogyne incognita eggs leads to irregular growth and embryonic lethality. Int J Parasitol. 2010;40: 1303–10.CrossRefPubMedGoogle Scholar
  25. 25.
    Wu Q, Song R, Ortogero N, et al. The RNase III enzyme DROSHA is essential for microRNA production and spermatogenesis. J Biol Chem. 2012;287:25173–90.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Bernstein E, Caudy AA, Hammond SM, Hannon GJ. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 2001;409:363–6.CrossRefPubMedGoogle Scholar
  27. 27.
    Han J, Lee Y, Yeom K-H, Kim Y-K, Jin H, Kim VN. The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev. 2004;18:3016–27.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Wilson DI, Burn J, Scambler P, Goodship J. DiGeorge syndrome: part of CATCH 22. J Med Genet. 1993;30:852–6.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Shiohama A, Sasaki T, Noda S, Minoshima S, Shimizu N. Molecular cloning and expression analysis of a novel gene DGCR8 located in the DiGeorge syndrome chromosomal region. Biochem Biophys Res Commun. 2003;304:184–90.CrossRefPubMedGoogle Scholar
  30. 30.
    Denli AM, Tops BBJ, Plasterk RHA, Ketting RF, Hannon GJ. Processing of primary microRNAs by the microprocessor complex. Nature. 2004;432:231–5.CrossRefPubMedGoogle Scholar
  31. 31.
    Landthaler M, Yalcin A, Tuschl T. The human DiGeorge syndrome critical region gene 8 and its D. melanogaster homolog are required for miRNA biogenesis. Curr Biol. 2004;14:2162–7.CrossRefPubMedGoogle Scholar
  32. 32.
    Zeng Y, Yi R, Cullen BR. Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha. EMBO J. 2005;24:138–48.CrossRefPubMedGoogle Scholar
  33. 33.
    Han J, Lee Y, Yeom K-H, Nam J-W, Heo I, Rhee J-K, Sohn SY, Cho Y, Zhang B-T, Kim VN. Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell. 2006;125:887–901.CrossRefPubMedGoogle Scholar
  34. 34.
    Mueller GA, Miller MT, Derose EF, Ghosh M, London RE, Hall TMT. Solution structure of the Drosha double-stranded RNA-binding domain. Silence. 2010;1:2.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Sohn SY, Bae WJ, Kim JJ, Yeom K-H, Kim VN, Cho Y. Crystal structure of human DGCR8 core. Nat Struct Mol Biol. 2007;14:847–53.CrossRefPubMedGoogle Scholar
  36. 36.
    Senturia R, Faller M, Yin S, Loo JA, Cascio D, Sawaya MR, Hwang D, Clubb RT, Guo F. Structure of the dimerization domain of DiGeorge critical region 8. Protein Sci. 2010;19: 1354–65.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Faller M, Matsunaga M, Yin S, Loo JA, Guo F. Heme is involved in microRNA processing. Nat Struct Mol Biol. 2007;14:23–9.CrossRefPubMedGoogle Scholar
  38. 38.
    Brownawell AM, Macara IG. Exportin-5, a novel karyopherin, mediates nuclear export of double-stranded RNA binding proteins. J Cell Biol. 2002;156:53–64.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Lund E, Güttinger S, Calado A, Dahlberg JE, Kutay U. Nuclear export of microRNA precursors. Science. 2004;303:95–8.CrossRefPubMedGoogle Scholar
  40. 40.
    Yi R, Qin Y, Macara IG, Cullen BR. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev. 2003;17:3011–6.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Bohnsack MT, Czaplinski K, Gorlich D. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA. 2004;10:185–91.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Gwizdek C, Ossareh-Nazari B, Brownawell AM, Doglio A, Bertrand E, Macara IG, Dargemont C. Exportin-5 mediates nuclear export of minihelix-containing RNAs. J Biol Chem. 2003;278: 5505–8.CrossRefPubMedGoogle Scholar
  43. 43.
    Gwizdek C, Bertrand E, Dargemont C, Lefebvre JC, Blanchard JM, Singer RH, Doglio A. Terminal minihelix, a novel RNA motif that directs polymerase III transcripts to the cell cytoplasm. Terminal minihelix and RNA export. J Biol Chem. 2001;276:25910–8.CrossRefPubMedGoogle Scholar
  44. 44.
    Lu S, Cullen BR. Adenovirus VA1 noncoding RNA can inhibit small interfering RNA and MicroRNA biogenesis. J Virol. 2004;78:12868–76.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Bischoff FR, Krebber H, Kempf T, Hermes I, Ponstingl H. Human RanGTPase-activating protein RanGAP1 is a homologue of yeast Rna1p involved in mRNA processing and transport. Proc Natl Acad Sci U S A. 1995;92:1749–53.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Bischoff FR, Ponstingl H. Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1. Nature. 1991;354:80–2.CrossRefPubMedGoogle Scholar
  47. 47.
    Zeng Y, Cullen BR. Structural requirements for pre-microRNA binding and nuclear export by Exportin 5. Nucleic Acids Res. 2004;32:4776–85.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Okada C, Yamashita E, Lee SJ, Shibata S, Katahira J, Nakagawa A, Yoneda Y, Tsukihara T. A high-resolution structure of the pre-microRNA nuclear export machinery. Science. 2009;326: 1275–9.CrossRefPubMedGoogle Scholar
  49. 49.
    Provost P, Dishart D, Doucet J, Frendewey D, Samuelsson B, Rådmark O. Ribonuclease activity and RNA binding of recombinant human Dicer. EMBO J. 2002;21:5864–74.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Zhang H, Kolb FA, Brondani V, Billy E, Filipowicz W. Human Dicer preferentially cleaves dsRNAs at their termini without a requirement for ATP. EMBO J. 2002;21:5875–85.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Humphreys DT, Hynes CJ, Patel HR, Wei GH, Cannon L, Fatkin D, Suter CM, Clancy JL, Preiss T. Complexity of murine cardiomyocyte miRNA biogenesis, sequence variant expression and function. PLoS One. 2012;7, e30933.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Grishok A, Pasquinelli AE, Conte D, Li N, Parrish S, Ha I, Baillie DL, Fire A, Ruvkun G, Mello CC. 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.CrossRefPubMedGoogle Scholar
  53. 53.
    Hutvágner G, McLachlan J, Pasquinelli AE, Bálint E, Tuschl T, Zamore PD. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science. 2001;293:834–8.CrossRefPubMedGoogle Scholar
  54. 54.
    Ketting RF, Fischer SE, Bernstein E, Sijen T, Hannon GJ, Plasterk RH. Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev. 2001;15:2654–9.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Bernstein E, Kim SY, Carmell MA, Murchison EP, Alcorn H, Li MZ, Mills AA, Elledge SJ, Anderson KV, Hannon GJ. Dicer is essential for mouse development. Nat Genet. 2003;35:215–7.CrossRefPubMedGoogle Scholar
  56. 56.
    Hatfield SD, Shcherbata HR, Fischer KA, Nakahara K, Carthew RW, Ruohola-Baker H. Stem cell division is regulated by the microRNA pathway. Nature. 2005;435:974–8.CrossRefPubMedGoogle Scholar
  57. 57.
    Ma J-B, Ye K, Patel DJ. Structural basis for overhang-specific small interfering RNA recognition by the PAZ domain. Nature. 2004;429:318–22.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Zhang H, Kolb FA, Jaskiewicz L, Westhof E, Filipowicz W. Single processing center models for human Dicer and bacterial RNase III. Cell. 2004;118:57–68.CrossRefPubMedGoogle Scholar
  59. 59.
    MacRae IJ, Zhou K, Li F, Repic A, Brooks AN, Cande WZ, Adams PD, Doudna JA. Structural basis for double-stranded RNA processing by Dicer. Science. 2006;311:195–8.CrossRefPubMedGoogle Scholar
  60. 60.
    Basyuk E, Suavet F, Doglio A, Bordonné R, Bertrand E. Human let-7 stem-loop precursors harbor features of RNase III cleavage products. Nucleic Acids Res. 2003;31:6593–7.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Cenik ES, Fukunaga R, Lu G, Dutcher R, Wang Y, Tanaka Hall TM, Zamore PD. Phosphate and R2D2 restrict the substrate specificity of Dicer-2, an ATP-driven ribonuclease. Mol Cell. 2011;42:172–84.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    MacRae IJ, Zhou K, Doudna JA. Structural determinants of RNA recognition and cleavage by Dicer. Nat Struct Mol Biol. 2007;14:934–40.CrossRefPubMedGoogle Scholar
  63. 63.
    Lau P-W, Potter CS, Carragher B, MacRae IJ. Structure of the human Dicer-TRBP complex by electron microscopy. Structure. 2009;17:1326–32.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Wang H-W, Noland C, Siridechadilok B, Taylor DW, Ma E, Felderer K, Doudna JA, Nogales E. Structural insights into RNA processing by the human RISC-loading complex. Nat Struct Mol Biol. 2009;16:1148–53.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Lau P-W, Guiley KZ, De N, Potter CS, Carragher B, MacRae IJ. The molecular architecture of human Dicer. Nat Struct Mol Biol. 2012;19:436–40.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Park J-E, Heo I, Tian Y, Simanshu DK, Chang H, Jee D, Patel DJ, Kim VN. Dicer recognizes the 5′ end of RNA for efficient and accurate processing. Nature. 2011;475:201–5.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Gu S, Jin L, Zhang Y, Huang Y, Zhang F, Valdmanis PN, Kay MA. The loop position of shRNAs and pre-miRNAs is critical for the accuracy of dicer processing in vivo. Cell. 2012;151:900–11.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Hammond SM, Boettcher S, Caudy AA, Kobayashi R, Hannon GJ. Argonaute2, a link between genetic and biochemical analyses of RNAi. Science. 2001;293:1146–50.CrossRefPubMedGoogle Scholar
  69. 69.
    Khvorova A, Reynolds A, Jayasena SD. Functional siRNAs and miRNAs exhibit strand bias. Cell. 2003;115:209–16.CrossRefPubMedGoogle Scholar
  70. 70.
    Schwarz DS, Hutvágner G, Du T, Xu Z, Aronin N, Zamore PD. Asymmetry in the assembly of the RNAi enzyme complex. Cell. 2003;115:199–208.CrossRefPubMedGoogle Scholar
  71. 71.
    Tokumaru S, Suzuki M, Yamada H, Nagino M, Takahashi T. let-7 regulates Dicer expression and constitutes a negative feedback loop. Carcinogenesis. 2008;29:2073–7.CrossRefPubMedGoogle Scholar
  72. 72.
    Lai EC. Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation. Nat Genet. 2002;30:363–4.CrossRefPubMedGoogle Scholar
  73. 73.
    Friedman RC, Farh KK-H, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009;19:92–105.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Hutvágner G, Zamore PD. A microRNA in a multiple-turnover RNAi enzyme complex. Science. 2002;297:2056–60.CrossRefPubMedGoogle Scholar
  75. 75.
    Yekta S, Shih I-H, Bartel DP. MicroRNA-directed cleavage of HOXB8 mRNA. Science. 2004;304:594–6.CrossRefPubMedGoogle Scholar
  76. 76.
    Zeng Y, Yi R, Cullen BR. MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc Natl Acad Sci U S A. 2003;100:9779–84.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Bhattacharyya SN, Habermacher R, Martine U, Closs EI, Filipowicz W. Relief of microRNA-mediated translational repression in human cells subjected to stress. Cell. 2006;125:1111–24.CrossRefPubMedGoogle Scholar
  78. 78.
    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;15:185–97.CrossRefPubMedGoogle Scholar
  79. 79.
    Pillai RS, Bhattacharyya SN, Filipowicz W. Repression of protein synthesis by miRNAs: how many mechanisms? Trends Cell Biol. 2007;17:118–26.CrossRefPubMedGoogle Scholar
  80. 80.
    Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet. 2008;9:102–14.CrossRefPubMedGoogle Scholar
  81. 81.
    Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116: 281–97.CrossRefPubMedGoogle Scholar
  82. 82.
    Krek A, Grün D, Poy MN, et al. Combinatorial microRNA target predictions. Nat Genet. 2005; 37:495–500.CrossRefPubMedGoogle Scholar
  83. 83.
    Chendrimada TP, Gregory RI, Kumaraswamy E, Norman J, Cooch N, Nishikura K, Shiekhattar R. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature. 2005;436:740–4.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Haase AD, Jaskiewicz L, Zhang H, Lainé S, Sack R, Gatignol A, Filipowicz W. TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts with Dicer and functions in RNA silencing. EMBO Rep. 2005;6:961–7.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM, Song J-J, Hammond SM, Joshua-Tor L, Hannon GJ. Argonaute2 is the catalytic engine of mammalian RNAi. Science. 2004;305: 1437–41.CrossRefPubMedGoogle Scholar
  86. 86.
    Swarts DC, Makarova K, Wang Y, Nakanishi K, Ketting RF, Koonin EV, Patel DJ, van der Oost J. The evolutionary journey of Argonaute proteins. Nat Struct Mol Biol. 2014;21:743–53.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Rivas FV, Tolia NH, Song J-J, Aragon JP, Liu J, Hannon GJ, Joshua-Tor L. Purified Argonaute2 and an siRNA form recombinant human RISC. Nat Struct Mol Biol. 2005;12:340–9.CrossRefPubMedGoogle Scholar
  88. 88.
    Schürmann N, Trabuco LG, Bender C, Russell RB, Grimm D. Molecular dissection of human Argonaute proteins by DNA shuffling. Nat Struct Mol Biol. 2013;20:818–26.CrossRefPubMedGoogle Scholar
  89. 89.
    Alisch RS, Jin P, Epstein M, Caspary T, Warren ST. Argonaute2 is essential for mammalian gastrulation and proper mesoderm formation. PLoS Genet. 2007;3, e227.CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Morita S, Horii T, Kimura M, Goto Y, Ochiya T, Hatada I. One Argonaute family member, Eif2c2 (Ago2), is essential for development and appears not to be involved in DNA methylation. Genomics. 2007;89:687–96.CrossRefPubMedGoogle Scholar
  91. 91.
    Cheloufi S, Dos Santos CO, Chong MMW, Hannon GJ. A dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature. 2010;465:584–9.CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Yang J-S, Maurin T, Robine N, Rasmussen KD, Jeffrey KL, Chandwani R, Papapetrou EP, Sadelain M, O’Carroll D, Lai EC. Conserved vertebrate mir-451 provides a platform for Dicer-independent, Ago2-mediated microRNA biogenesis. Proc Natl Acad Sci U S A. 2010;107: 15163–8.CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Schirle NT, MacRae IJ. The crystal structure of human Argonaute2. Science. 2012;336: 1037–40.CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Elkayam E, Kuhn C-D, Tocilj A, Haase AD, Greene EM, Hannon GJ, Joshua-Tor L. The structure of human Argonaute-2 in complex with miR-20a. Cell. 2012;150:100–10.CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15–20.CrossRefPubMedGoogle Scholar
  96. 96.
    Ma J-B, Yuan Y-R, Meister G, Pei Y, Tuschl T, Patel DJ. Structural basis for 5′-end-specific recognition of guide RNA by the A. fulgidus Piwi protein. Nature. 2005;434:666–70.CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Frank F, Sonenberg N, Nagar B. Structural basis for 5′-nucleotide base-specific recognition of guide RNA by human AGO2. Nature. 2010;465:818–22.CrossRefPubMedGoogle Scholar
  98. 98.
    Landthaler M, Gaidatzis D, Rothballer A, Chen PY, Soll SJ, Dinic L, Ojo T, Hafner M, Zavolan M, Tuschl T. Molecular characterization of human Argonaute-containing ribonucleoprotein complexes and their bound target mRNAs. RNA. 2008;14:2580–96.CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Höck J, Weinmann L, Ender C, Rüdel S, Kremmer E, Raabe M, Urlaub H, Meister G. Proteomic and functional analysis of Argonaute-containing mRNA-protein complexes in human cells. EMBO Rep. 2007;8:1052–60.CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Liu J, Rivas FV, Wohlschlegel J, Yates JR, Parker R, Hannon GJ. A role for the P-body component GW182 in microRNA function. Nat Cell Biol. 2005;7:1261–6.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Development, Aging and Regeneration ProgramSanford Burnham Prebys Medical Discovery InstituteLa JollaUSA
  2. 2.Department of Physiology, Anatomy and GeneticsUniversity of OxfordOxfordUK

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