title: Molecular mechanisms of RNA interference.
abstract: Small RNA molecules regulate eukaryotic gene expression during development and in response to stresses including viral infection. Specialized ribonucleases and RNA-binding proteins govern the production and action of small regulatory RNAs. After initial processing in the nucleus by Drosha, precursor microRNAs (pre-miRNAs) are transported to the cytoplasm, where Dicer cleavage generates mature microRNAs (miRNAs) and short interfering RNAs (siRNAs). These double-stranded products assemble with Argonaute proteins such that one strand is preferentially selected and used to guide sequence-specific silencing of complementary target mRNAs by endonucleolytic cleavage or translational repression. Molecular structures of Dicer and Argonaute proteins, and of RNA-bound complexes, have offered exciting insights into the mechanisms operating at the heart of RNA-silencing pathways.
authors: Howard Hughes Medical Institute.
authors: Ross C
authors: RC
authors: Wilson
authors: Jennifer A
authors: JA
authors: Doudna
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000737:chemistry / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism
chemical_list: D060565:Argonaute Proteins; D035683:MicroRNAs; D034741:RNA, Small Interfering; D043244:Ribonuclease III
references: EMBO J. 2005 Jan 12;24(1):138-48
references: 15565168
references: Cell. 2011 Jul 22;146(2):262-76
references: 21784247
references: Curr Genomics. 2010 Nov;11(7):537-61
references: 21532838
references: RNA Biol. 2008 Apr-Jun;5(2):92-103
references: 18421256
references: Adv Exp Med Biol. 2011;700:140-55
references: 21755479
references: Science. 2012 Apr 13;336(6078):237-40
references: 22499947
references: Cell. 2009 Feb 20;136(4):642-55
references: 19239886
references: RNA. 2010 Aug;16(8):1570-83
references: 20558544
references: Nature. 2001 Jan 18;409(6818):363-6
references: 11201747
references: J Mol Biol. 2012 Sep 28;422(4):466-76
references: 22727743
references: Nature. 2005 Mar 31;434(7033):663-6
references: 15800628
references: Science. 2011 Feb 4;331(6017):550-3
references: 21292970
references: Nat Rev Genet. 2011 Nov 18;12(12):846-60
references: 22094948
references: Nat Struct Mol Biol. 2008 Apr;15(4):346-53
references: 18345015
references: EMBO J. 2004 Dec 8;23(24):4727-37
references: 15565169
references: J Struct Biol. 2002 Oct-Dec;140(1-3):147-53
references: 12490163
references: FEBS Lett. 2008 Aug 6;582(18):2753-60
references: 18625233
references: Nature. 2003 Nov 27;426(6965):468-74
references: 14615802
references: Mol Cell. 2011 Apr 22;42(2):172-84
references: 21419681
references: Cell. 2012 Jul 6;150(1):100-10
references: 22682761
references: Science. 2012 Apr 13;336(6078):233-7
references: 22422859
references: Science. 2012 May 25;336(6084):1037-40
references: 22539551
references: Science. 2004 Nov 19;306(5700):1377-80
references: 15550672
references: Science. 2004 Sep 3;305(5689):1434-7
references: 15284453
references: Nat Struct Mol Biol. 2012 Jun 05;19(6):586-93
references: 22664986
references: Nature. 2010 Aug 12;466(7308):835-40
references: 20703300
references: Science. 2006 Jan 13;311(5758):195-8
references: 16410517
references: EMBO J. 2007 Feb 7;26(3):775-83
references: 17255951
references: Cell. 2006 Jun 2;125(5):887-901
references: 16751099
references: Trends Biochem Sci. 2010 Jul;35(7):368-76
references: 20395147
references: Silence. 2010 Jan 12;1(1):2
references: 20226070
references: Genes Dev. 2007 Mar 1;21(5):590-600
references: 17311884
references: Nucleic Acids Res. 2005 Feb 07;33(3):807-15
references: 15699182
references: Sci STKE. 2007 Jan 02;2007(367):re1
references: 17200520
references: Nat Struct Mol Biol. 2010 Feb;17(2):238-40
references: 20098421
references: Proc Natl Acad Sci U S A. 2011 Jun 28;108(26):10466-71
references: 21646546
references: EMBO J. 2006 Feb 8;25(3):522-32
references: 16424907
references: EMBO J. 2002 Nov 1;21(21):5875-85
references: 12411505
references: Nat Struct Mol Biol. 2011 Sep 18;18(10):1153-8
references: 21926993
references: RNA. 2009 Dec;15(12):2219-35
references: 19861421
references: Nature. 2009 Oct 8;461(7265):823-7
references: 19812675
references: Nature. 2012 Jun 20;486(7403):368-74
references: 22722195
references: Nucleic Acids Res. 2008 Nov;36(20):6511-22
references: 18927112
references: Biochem Soc Trans. 2010 Feb;38(Pt 1):242-51
references: 20074068
references: Nature. 2009 Oct 8;461(7265):754-61
references: 19812667
references: BMC Genomics. 2009 Sep 04;10:413
references: 19732433
references: Trends Ecol Evol. 2008 Oct;23(10):578-87
references: 18715673
references: J Cell Sci. 2012 Jun 1;125(Pt 11):2709-20
references: 22393237
references: Curr Biol. 2006 Mar 7;16(5):530-5
references: 16527750
references: Gene. 2007 Jul 15;396(2):312-20
references: 17482383
references: BMC Evol Biol. 2009 Apr 28;9:85
references: 19400936
references: Protein Sci. 2010 Jul;19(7):1354-65
references: 20506313
references: Nature. 2004 May 20;429(6989):318-322
references: 15152257
references: J Biol Chem. 2005 Jul 29;280(30):27595-603
references: 15932881
references: Annu Rev Biochem. 2010;79:351-79
references: 20533884
references: Nat Struct Mol Biol. 2007 Sep;14(9):847-53
references: 17704815
references: Mol Cell. 2011 Jul 8;43(1):110-21
references: 21726814
references: J Mol Biol. 2008 Jun 27;380(1):237-43
references: 18508075
references: Cell. 2009 Oct 2;139(1):112-22
references: 19804757
references: Mol Cell. 2009 Jan 30;33(2):204-14
references: 19187762
references: Nature. 2008 Dec 18;456(7224):921-6
references: 19092929
references: Nat Struct Mol Biol. 2011 Jun;18(6):650-7
references: 21552258
references: Nat Struct Mol Biol. 2007 Oct;14(10):897-903
references: 17891150
references: Cell. 2006 Jan 27;124(2):355-66
references: 16439209
references: Nat Struct Mol Biol. 2009 Nov;16(11):1148-53
references: 19820710
references: Curr Opin Struct Biol. 2007 Feb;17(1):138-45
references: 17194582
references: EMBO Rep. 2004 Feb;5(2):189-94
references: 14749716
references: Nat Struct Mol Biol. 2004 Jun;11(6):576-7
references: 15156196
references: EMBO Rep. 2010 Jul;11(7):522-7
references: 20539312
references: Cell. 2005 Jan 14;120(1):15-20
references: 15652477
references: Nucleic Acids Res. 2011 Mar;39(4):1510-25
references: 20972213
references: Nature. 2003 Sep 25;425(6956):415-9
references: 14508493
references: Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17719-24
references: 17965236
references: Nucleic Acids Res. 2011 May;39(9):3836-51
references: 21245036
references: Nature. 2008 Nov 13;456(7219):209-13
references: 18754009
references: PLoS One. 2008;3(10):e3420
references: 18923704
references: Nat Struct Mol Biol. 2011 Jun;18(6):658-64
references: 21552261
references: Cell. 2005 Nov 18;123(4):607-20
references: 16271386
references: Science. 2007 Mar 16;315(5818):1587-90
references: 17322028
references: Mol Cell Biol. 2011 Feb;31(4):884-96
references: 21135122
references: Nature. 2009 Jan 22;457(7228):405-12
references: 19158786
references: Cell. 2003 Oct 17;115(2):199-208
references: 14567917
references: Protein Sci. 2011 Jan;20(1):118-30
references: 21080422
references: Nat Struct Mol Biol. 2012 Mar 18;19(4):436-40
references: 22426548
references: Nature. 2004 Nov 11;432(7014):235-40
references: 15531877
references: Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):512-7
references: 18178619
references: Nucleic Acids Res. 2007;35(15):5154-64
references: 17660190
references: RNA. 2009 Jun;15(6):1078-89
references: 19398495
references: Nat Struct Mol Biol. 2006 Sep;13(9):787-92
references: 16936728
references: RNA. 2003 Sep;9(9):1034-48
references: 12923253
references: Cell. 2011 Oct 14;147(2):423-35
references: 22000019
references: Nature. 2010 Jun 10;465(7299):818-22
references: 20505670
references: Cold Spring Harb Symp Quant Biol. 2006;71:59-66
references: 17381281
references: Nat Rev Genet. 2011 May;12(5):329-40
references: 21499294
references: RNA. 2010 Mar;16(3):474-81
references: 20106953
references: Mol Cell. 2011 Mar 4;41(5):589-99
references: 21362554
references: Mol Cell Biol. 2009 Jun;29(12):3243-54
references: 19349299
references: BMC Mol Biol. 2009 May 07;10:38
references: 19422693