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The microRNA Machinery

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 887))

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.

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References

  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.

    Article  CAS  PubMed  Google Scholar 

  2. Roberts TC, Wood MJA. Therapeutic targeting of non-coding RNAs. Essays Biochem. 2013; 54:127–45.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gilad S, Meiri E, Yogev Y, et al. Serum microRNAs are promising novel biomarkers. PLoS One. 2008;3, e3148.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kim Y-K, Kim VN. Processing of intronic microRNAs. EMBO J. 2007;26:775–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science. 2001;294:853–8.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  15. Doench JG, Sharp PA. Specificity of microRNA target selection in translational repression. Genes Dev. 2004;18:504–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Guo H, Ingolia NT, Weissman JS, Bartel DP. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010;466:835–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell. 2005;123:631–40.

    Article  CAS  PubMed  Google Scholar 

  19. Roberts TC. The microRNA biology of the mammalian nucleus. Mol Ther Nucleic Acids. 2014;3:e188

    Google Scholar 

  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. 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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  23. Lee Y, Ahn C, Han J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003;425:415–9.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wilson DI, Burn J, Scambler P, Goodship J. DiGeorge syndrome: part of CATCH 22. J Med Genet. 1993;30:852–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  30. Denli AM, Tops BBJ, Plasterk RHA, Ketting RF, Hannon GJ. Processing of primary microRNAs by the microprocessor complex. Nature. 2004;432:231–5.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Lund E, Güttinger S, Calado A, Dahlberg JE, Kutay U. Nuclear export of microRNA precursors. Science. 2004;303:95–8.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  44. Lu S, Cullen BR. Adenovirus VA1 noncoding RNA can inhibit small interfering RNA and MicroRNA biogenesis. J Virol. 2004;78:12868–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Bischoff FR, Ponstingl H. Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1. Nature. 1991;354:80–2.

    Article  CAS  PubMed  Google Scholar 

  47. Zeng Y, Cullen BR. Structural requirements for pre-microRNA binding and nuclear export by Exportin 5. Nucleic Acids Res. 2004;32:4776–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. MacRae IJ, Zhou K, Doudna JA. Structural determinants of RNA recognition and cleavage by Dicer. Nat Struct Mol Biol. 2007;14:934–40.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  69. Khvorova A, Reynolds A, Jayasena SD. Functional siRNAs and miRNAs exhibit strand bias. Cell. 2003;115:209–16.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  72. Lai EC. Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation. Nat Genet. 2002;30:363–4.

    Article  CAS  PubMed  Google Scholar 

  73. Friedman RC, Farh KK-H, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009;19:92–105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Hutvágner G, Zamore PD. A microRNA in a multiple-turnover RNAi enzyme complex. Science. 2002;297:2056–60.

    Article  PubMed  Google Scholar 

  75. Yekta S, Shih I-H, Bartel DP. MicroRNA-directed cleavage of HOXB8 mRNA. Science. 2004;304:594–6.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  79. Pillai RS, Bhattacharyya SN, Filipowicz W. Repression of protein synthesis by miRNAs: how many mechanisms? Trends Cell Biol. 2007;17:118–26.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  81. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116: 281–97.

    Article  CAS  PubMed  Google Scholar 

  82. Krek A, Grün D, Poy MN, et al. Combinatorial microRNA target predictions. Nat Genet. 2005; 37:495–500.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Schirle NT, MacRae IJ. The crystal structure of human Argonaute2. Science. 2012;336: 1037–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

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Roberts, T.C. (2015). The microRNA Machinery. In: Santulli, G. (eds) microRNA: Basic Science. Advances in Experimental Medicine and Biology, vol 887. Springer, Cham. https://doi.org/10.1007/978-3-319-22380-3_2

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