The mechanics of miRNA-mediated gene silencing: A look under the hood of miRISC

Nature Structural and Molecular Biology

Volumn 19, Issue 6, 2012, Pages 586-593

  Fabian, Marc R ^a   Sonenberg, Nahum ^a  

^a MCGILL UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ARGONAUTE PROTEIN; CHEMOKINE RECEPTOR CCR4; HUR PROTEIN; MICRORNA; MICRORNA INDUCED SILENCING COMPLEX; POLYADENYLIC ACID BINDING PROTEIN; UNCLASSIFIED DRUG;

3' UNTRANSLATED REGION; CAENORHABDITIS ELEGANS; DROSOPHILA MELANOGASTER; GENE REPRESSION; GENE SILENCING; HUMAN; ISOTOPE LABELING; NONHUMAN; POSTTRANSCRIPTIONAL GENE SILENCING; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN MOTIF; REVIEW; RIBOSOME; RNA SYNTHESIS; RNA TRANSLATION; ZEBRA FISH;

ANIMALS; GENE SILENCING; HUMANS; MICRORNAS; PROTEIN BIOSYNTHESIS; RNA-BINDING PROTEINS;

EID: 84861866572     PISSN: 15459993     EISSN: 15459985     Source Type: Journal    
DOI: 10.1038/nsmb.2296     Document Type: Review

References (102)

1. Bartel, D.P. MicroRNAs: target recognition and regulatory functions. Cell 136, 215-233 (2009).
2. Fabian, M.R., Sonenberg, N. & Filipowicz, W. Regulation of mRNA translation and stability by microRNAs. Annu. Rev. Biochem. 79, 351-379 (2010).
3. Eulalio, A., Huntzinger, E. & Izaurralde, E. Getting to the root of miRNA-mediated gene silencing. Cell 132, 9-14 (2008).
4. Sonenberg, N. & Hinnebusch, A.G. Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell 136, 731-745 (2009).
5. Wang, B., Yanez, A. & Novina, C.D. MicroRNA-repressed mRNAs contain 40S but not 60S components. Proc. Natl. Acad. Sci. USA 105, 5343-5348 (2008).
6. Humphreys, D.T., Westman, B.J., Martin, D.I. & Preiss, T. MicroRNAs control translation initiation by inhibiting eukaryotic initiation factor 4E/cap and poly(A) tail function. Proc. Natl. Acad. Sci. USA 102, 16961-16966 (2005).
7. Thermann, R. & Hentze, M.W. Drosophila miR2 induces pseudo-polysomes and inhibits translation initiation. Nature 447, 875-878 (2007).
8. Mathonnet, G. et al. MicroRNA inhibition of translation initiation in vitro by targeting the cap-binding complex eIF4F. Science 317, 1764-1767 (2007).
9. Pillai, R.S. et al. Inhibition of translational initiation by Let-7 MicroRNA in human cells. Science 309, 1573-1576 (2005).
10. Nottrott, S., Simard, M.J. & Richter, J.D. Human let-7a miRNA blocks protein production on actively translating polyribosomes. Nat. Struct. Mol. Biol. 13, 1108-1114 (2006).
11. Petersen, C.P., Bordeleau, M.E., Pelletier, J. & Sharp, P.A. Short RNAs repress translation after initiation in mammalian cells. Mol. Cell 21, 533-542 (2006).
12. Olsen, P.H. & 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. 216, 671-680 (1999).
13. Maroney, P.A., Yu, Y., Fisher, J. & Nilsen, T.W. Evidence that microRNAs are associated with translating messenger RNAs in human cells. Nat. Struct. Mol. Biol. 13, 1102-1107 (2006).
14. Wu, L., Fan, J. & Belasco, J.G. MicroRNAs direct rapid deadenylation of mRNA. Proc. Natl. Acad. Sci. USA 103, 4034-4039 (2006).
15. Chen, C.Y., Zheng, D., Xia, Z. & Shyu, A.B. Ago-TNRC6 triggers microRNA-mediated decay by promoting two deadenylation steps. Nat. Struct. Mol. Biol. 16, 1160-1166 (2009).
16. Giraldez, A.J. et al. Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science 312, 75-79 (2006). The first demonstration of miRNA-mediated deadenylation in any organism.
17. Behm-Ansmant, I. et al. mRNA degradation by miRNAs and GW182 requires both CCR4:NOT deadenylase and DCP1:DCP2 decapping complexes. Genes Dev. 20, 1885-1898 (2006).
18. 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 11, 1640-1647 (2005).
19. Bartel, D.P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281-297 (2004).
20. Song, J.J., Smith, S.K., Hannon, G.J. & Joshua-Tor, L. Crystal structure of Argonaute and its implications for RISC slicer activity. Science 305, 1434-1437 (2004).
21. Schmitter, D. et al. Effects of Dicer and Argonaute down-regulation on mRNA levels in human HEK293 cells. Nucleic Acids Res. 34, 4801-4815 (2006).
22. Pillai, R.S., Artus, C.G. & Filipowicz, W. Tethering of human Ago proteins to mRNA mimics the miRNA-mediated repression of protein synthesis. RNA 10, 1518-1525 (2004).
23. Eulalio, A., Huntzinger, E. & Izaurralde, E. GW182 interaction with Argonaute is essential for miRNA-mediated translational repression and mRNA decay. Nat. Struct. Mol. Biol. 15, 346-353 (2008).
24. Yao, B., Li, S., Lian, S.L., Fritzler, M.J. & Chan, E.K. Mapping of Ago2-GW182 functional interactions. Methods Mol. Biol. 725, 45-62 (2011).
25. Till, S. et al. A conserved motif in Argonaute-interacting proteins mediates functional interactions through the Argonaute PIWI domain. Nat. Struct. Mol. Biol. 14, 897-903 (2007).
26. Fabian, M.R. et al. Mammalian miRNA RISC recruits CAF1 and PABP to affect PABP-dependent deadenylation. Mol. Cell 35, 868-880 (2009).
27. Takimoto, K., Wakiyama, M. & Yokoyama, S. Mammalian GW182 contains multiple Argonaute-binding sites and functions in microRNA-mediated translational repression. RNA 15, 1078-1089 (2009).
28. Eulalio, A., Tritschler, F. & Izaurralde, E. The GW182 protein family in animal cells: new insights into domains required for miRNA-mediated gene silencing. RNA 15, 1433-1442 (2009).
29. El-Shami, M. et al. Reiterated WG/GW motifs form functionally and evolutionarily conserved ARGONAUTE-binding platforms in RNAi-related components. Genes Dev. 21, 2539-2544 (2007).
30. Lian, S.L. et al. The C-terminal half of human Ago2 binds to multiple GW-rich regions of GW182 and requires GW182 to mediate silencing. RNA 15, 804-813 (2009).
31. Chekulaeva, M. et al. miRNA repression involves GW182-mediated recruitment of CCR4-NOT through conserved W-containing motifs. Nat. Struct. Mol. Biol. 18, 1218-1226 (2011). References 31, 40 and 45 report how GW182 recruits the deadenylation machineries to effect miRNA-mediated silencing.
32. Chekulaeva, M., Parker, R. & Filipowicz, W. The GW/WG repeats of Drosophila GW182 function as effector motifs for miRNA-mediated repression. Nucleic Acids Res. 38, 6673-6683 (2010).
33. Eulalio, A. et al. The RRM domain in GW182 proteins contributes to miRNA-mediated gene silencing. Nucleic Acids Res. 37, 2974-2983 (2009).
34. Zipprich, J.T., Bhattacharyya, S., Mathys, H. & Filipowicz, W. Importance of the C-terminal domain of the human GW182 protein TNRC6C for translational repression. RNA 15, 781-793 (2009).
35. Chekulaeva, M., Filipowicz, W. & Parker, R. Multiple independent domains of dGW182 function in miRNA-mediated repression in Drosophila. RNA 15, 794-803 (2009).
36. Eulalio, A., Helms, S., Fritzsch, C., Fauser, M. & Izaurralde, E. A C-terminal silencing domain in GW182 is essential for miRNA function. RNA 15, 1067-1077 (2009).
37. Mishima, Y. et al. Translational inhibition by deadenylation-independent mechanisms is central to microRNA-mediated silencing in zebrafish. Proc. Natl. Acad. Sci. USA 109, 1104-1109 (2012).
38. Huntzinger, E., Braun, J.E., Heimstadt, S., Zekri, L. & Izaurralde, E. Two PABPC1-binding sites in GW182 proteins promote miRNA-mediated gene silencing. EMBO J. 29, 4146-4160 (2010).
39. Zekri, L., Huntzinger, E., Heimstadt, S. & Izaurralde, E. The silencing domain of GW182 interacts with PABPC1 to promote translational repression and degradation of microRNA targets and is required for target release. Mol. Cell. Biol. 29, 6220-6231 (2009).
40. Fabian, M.R. et al. miRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT. Nat. Struct. Mol. Biol. 18, 1211-1217 (2011).
41. Jinek, M., Fabian, M.R., Coyle, S.M., Sonenberg, N. & Doudna, J.A. Structural insights into the human GW182-PABC interaction in microRNA-mediated deadenylation. Nat. Struct. Mol. Biol. 17, 238-240 (2010).
42. Ding, L., Spencer, A., Morita, K. & Han, M. The developmental timing regulator AIN-1 interacts with miRISCs and may target the argonaute protein ALG-1 to cytoplasmic P bodies in C. elegans. Mol. Cell 19, 437-447 (2005).
43. Sen, G.L. & Blau, H.M. Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies. Nat. Cell Biol. 7, 633-636 (2005).
44. Liu, J. et al. A role for the P-body component GW182 in microRNA function. Nat. Cell Biol. 7, 1261-1266 (2005).
45. Braun, J.E., Huntzinger, E., Fauser, M. & Izaurralde, E. GW182 proteins directly recruit cytoplasmic deadenylase complexes to miRNA targets. Mol. Cell 44, 120-133 (2011).
46. Kuzuoglu-Oztürk, D., Huntzinger, E., Schmidt, S. & Izaurralde, E. The Caenorhabditis elegans GW182 protein AIN-1 interacts with PAB-1 and subunits of the PAN2-PAN3 and CCR4-NOT deadenylase complexes. Nucleic Acids Res. 10.1093/nar/gks218 (2012).
47. Derry, M.C., Yanagiya, A., Martineau, Y. & Sonenberg, N. Regulation of poly(A)-binding protein through PABP-interacting proteins. Cold Spring Harb. Symp. Quant. Biol. 71, 537-543 (2006).
48. Siddiqui, N., Osborne, M.J., Gallie, D.R. & Gehring, K. Solution structure of the PABC domain from wheat poly (A)-binding protein: an insight into RNA metabolic and translational control in plants. Biochemistry 46, 4221-4231 (2007).
49. Mauxion, F., Chen, C.Y., Seraphin, B. & Shyu, A.B. BTG/TOB factors impact deadenylases. Trends Biochem. Sci. 34, 640-647 (2009).
50. Kozlov, G. et al. Structure and function of the C-terminal PABC domain of human poly(A)-binding protein. Proc. Natl. Acad. Sci. USA 98, 4409-4413 (2001).
51. Kozlov, G., Safaee, N., Rosenauer, A. & Gehring, K. Structural basis of binding of P-body-associated proteins GW182 and ataxin-2 by the Mlle domain of poly(A)-binding protein. J. Biol. Chem. 285, 13599-13606 (2010).
52. Zhang, L. 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 28, 598-613 (2007).
53. Walters, R.W., Bradrick, S.S. & Gromeier, M. Poly(A)-binding protein modulates mRNA susceptibility to cap-dependent miRNA-mediated repression. RNA 16, 239-250 (2010).
54. Fukaya, T. & Tomari, Y. PABP is not essential for microRNA-mediated translational repression and deadenylation in vitro. EMBO J. 30, 4998-5009 (2011).
55. 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. 21, 1857-1862 (2007).
56. Wu, E. et al. Pervasive and cooperative deadenylation of 3′UTRs by embryonic microRNA families. Mol. Cell 40, 558-570 (2010).
57. Piao, X., Zhang, X., Wu, L. & Belasco, J.G. CCR4-NOT deadenylates mRNA associated with RNA-induced silencing complexes in human cells. Mol. Cell. Biol. 30, 1486-1494 (2010).
58. Su, H. et al. Mammalian hyperplastic discs homolog EDD regulates miRNA-mediated gene silencing. Mol. Cell 43, 97-109 (2011).
59. Coller, J. & Parker, R. General translational repression by activators of mRNA decapping. Cell 122, 875-886 (2005).
60. Chu, C.Y. & Rana, T.M. Translation repression in human cells by microRNA-induced gene silencing requires RCK/p54. PLoS Biol. 4, e210 (2006).
61. Lee, R.C., Feinbaum, R.L. & Ambros, V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843-854 (1993).
62. Bagga, S. et al. Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell 122, 553-563 (2005).
63. Lim, L.P. et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433, 769-773 (2005).
64. Bhattacharyya, S.N., Habermacher, R., Martine, U., Closs, E.I. & Filipowicz, W. Relief of microRNA-mediated translational repression in human cells subjected to stress. Cell 125, 1111-1124 (2006).The first demonstration that miRNA-mediated gene silencing is derepressed by an RNA-binding protein.
65. Ding, X.C. & Grosshans, H. Repression of C. elegans microRNA targets at the initiation level of translation requires GW182 proteins. EMBO J. 28, 213-222 (2009).
66. Eulalio, A. et al. Deadenylation is a widespread effect of miRNA regulation. RNA 15, 21-32 (2009).
67. Selbach, M. et al. Widespread changes in protein synthesis induced by microRNAs. Nature 455, 58-63 (2008).
68. Baek, D. et al. The impact of microRNAs on protein output. Nature 455, 64-71 (2008).
69. Yang, Y. et al. Identifying targets of miR-143 using a SILAC-based proteomic approach. Mol. Biosyst. 6, 1873-1882 (2010).
70. Guo, H., Ingolia, N.T., Weissman, J.S. & Bartel, D.P. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 466, 835-840 (2010).
71. Hendrickson, D.G. et al. Concordant regulation of translation and mRNA abundance for hundreds of targets of a human microRNA. PLoS Biol. 7, e1000238 (2009).
72. Banerjee, S., Neveu, P. & Kosik, K.S. A coordinated local translational control point at the synapse involving relief from silencing and MOV10 degradation. Neuron 64, 871-884 (2009).
73. Zdanowicz, A. et al. Drosophila miR2 primarily targets the m7GpppN cap structure for translational repression. Mol. Cell 35, 881-888 (2009).
74. Djuranovic, S., Nahvi, A. & Green, R. miRNA-mediated gene silencing by translational repression followed by mRNA deadenylation and decay. Science 336, 237-240 (2012).
75. Bazzini, A.A., Lee, M.T. & Giraldez, A.J. Ribosome profiling shows that miR-430 reduces translation before causing mRNA decay in zebrafish. Science 336, 233-237 (2012). Together with reference 74, the first in vivo demonstration that miRNA-mediated translational repression precedes mRNA decay.
76. Beilharz, T.H. & Preiss, T. Widespread use of poly(A) tail length control to accentuate expression of the yeast transcriptome. RNA 13, 982-997 (2007).
77. Djuranovic, S. et al. Allosteric regulation of Argonaute proteins by miRNAs. Nat. Struct. Mol. Biol. 17, 144-150 (2010).
78. Kiriakidou, M. et al. An mRNA m7G cap binding-like motif within human Ago2 represses translation. Cell 129, 1141-1151 (2007).
79. Djuranovic, S., Nahvi, A. & Green, R. A parsimonious model for gene regulation by miRNAs. Science 331, 550-553 (2011).
80. Kinch, L.N. & Grishin, N.V. The human Ago2 MC region does not contain an eIF4E-like mRNA cap binding motif. Biol. Direct 4, 2 (2009).
81. Frank, F. et al. Structural analysis of 5′-mRNA-cap interactions with the human AGO2 MID domain. EMBO Rep. 12, 415-420 (2011).
82. Cooke, A., Prigge, A. & Wickens, M. Translational repression by deadenylases. J. Biol. Chem. 285, 28506-28513 (2010). Shows that the CCR4-NOT complex represses cap-dependent translation in a deadenylation-independent manner.
83. Glorian, V. et al. HuR-dependent loading of miRNA RISC to the mRNA encoding the Ras-related small GTPase RhoB controls its translation during UV-induced apoptosis. Cell Death Differ. 18, 1692-1701 (2011).
84. Kim, H.H. et al. HuR recruits let-7/RISC to repress c-Myc expression. Genes Dev. 23, 1743-1748 (2009).
85. Kundu, P., Fabian, M.R., Sonenberg, N., Bhattacharyya, S. & Filipowicz, W. HuR protein attenuates miRNA-mediated repression by promoting miRISC dissociation from the target RNA. Nucleic Acids Res. 10.1093/nar/gks148 (2012).
86. Meisner, N.C. & Filipowicz, W. Properties of the regulatory RNA-binding protein HuR and its role in controlling miRNA repression. Adv. Exp. Med. Biol. 700, 106-123 (2011).
87. Tominaga, K. et al. Competitive regulation of nucleolin expression by HuR and miR-494. Mol. Cell. Biol. 31, 4219-4231 (2011).
88. Young, L.E., Moore, A.E., Sokol, L., Meisner-Kober, N. & Dixon, D.A. The mRNA stability factor HuR inhibits microRNA-16 Targeting of COX-2. Mol. Cancer Res. 10, 167-180 (2012).
89. Mishima, Y. et al. Differential regulation of germline mRNAs in soma and germ cells by zebrafish miR-430. Curr. Biol. 16, 2135-2142 (2006).
90. Kedde, M. et al. RNA-binding protein Dnd1 inhibits microRNA access to target mRNA. Cell 131, 1273-1286 (2007).
91. Nolde, M.J., Saka, N., Reinert, K.L. & Slack, F.J. The Caenorhabditis elegans pumilio homolog, puf-9, is required for the 3′UTR-mediated repression of the let-7 microRNA target gene, hbl-1. Dev. Biol. 305, 551-563 (2007).
92. Kedde, M. et al. A Pumilio-induced RNA structure switch in p27-3′UTR controls miR-221 and miR-222 accessibility. Nat. Cell Biol. 12, 1014-1020 (2010).
93. Henkin, T.M. Riboswitch RNAs: using RNA to sense cellular metabolism. Genes Dev. 22, 3383-3390 (2008).
94. Roth, A. & Breaker, R.R. The structural and functional diversity of metabolite-binding riboswitches. Annu. Rev. Biochem. 78, 305-334 (2009).
95. Galgano, A. et al. Comparative analysis of mRNA targets for human PUF-family proteins suggests extensive interaction with the miRNA regulatory system. PLoS ONE 3, e3164 (2008).
96. Goldstrohm, A.C., Hook, B.A., Seay, D.J. & Wickens, M. PUF proteins bind Pop2p to regulate messenger RNAs. Nat. Struct. Mol. Biol. 13, 533-539 (2006).
97. Mukherjee, N. et al. Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability. Mol. Cell 43, 327-339 (2011).
98. Lebedeva, S. et al. Transcriptome-wide analysis of regulatory interactions of the RNA-binding protein HuR. Mol. Cell 43, 340-352 (2011).
99. Yeap, B.B. et al. Novel binding of HuR and poly(C)-binding protein to a conserved UC-rich motif within the 3′-untranslated region of the androgen receptor messenger RNA. J. Biol. Chem. 277, 27183-27192 (2002).
100. Lastres-Becker, I., Rub, U. & Auburger, G. Spinocerebellar ataxia 2 (SCA2). Cerebellum 7, 115-124 (2008).
101. McCann, C. et al. The Ataxin-2 protein is required for microRNA function and synapse-specific long-term olfactory habituation. Proc. Natl. Acad. Sci. USA 108, E655-E662 (2011).
102. Moretti, F., Kaiser, C., Zdanowicz-Specht, A. & Hentze, M.W. PABP and the poly(A) tail augment microRNA repression by facilitated miRISC binding. Nat. Struct. Mol. Biol. published online, doi:10.1038/nsmb.2309 (27 May 2012).