title: The Ccr4-Not complex is a key regulator of eukaryotic gene expression.
abstract: The Ccr4-Not complex is a multisubunit complex present in all eukaryotes that contributes to regulate gene expression at all steps, from production of messenger RNAs (mRNAs) in the nucleus to their degradation in the cytoplasm. In the nucleus it influences the post-translational modifications of the chromatin template that has to be remodeled for transcription, it is present at sites of transcription and associates with transcription factors as well as with the elongating polymerase, it interacts with the factors that prepare the new transcript for export to the cytoplasm and finally is important for nuclear quality control and influences mRNA export. In the cytoplasm it is present in polysomes where mRNAs are translated and in RNA granules where mRNAs will be redirected upon inhibition of translation. It influences mRNA translatability, and is needed during translation, on one hand for co-translational protein interactions and on the other hand to preserve translation that stalls. It is one of the relevant players during co-translational quality control. It also interacts with factors that will repress translation or induce mRNA decapping when recruited to the translating template. Finally, Ccr4-Not carries deadenylating enzymes and is a key player in mRNA decay, generic mRNA decay that follows normal translation termination, co-translational mRNA decay of transcripts on which the ribosomes stall durably or which carry a non-sense mutation and finally mRNA decay that is induced by external signaling for a change in genetic programming. Ccr4-Not is a master regulator of eukaryotic gene expression. WIREs RNA 2016, 7:438-454. doi: 10.1002/wrna.1332 For further resources related to this article, please visit the WIREs website.
authors.affiliation: Department Microbiology and Molecular Medicine, CMU, Geneva, Switzerland.|Institute of Genetics and Genomics, Geneva, Switzerland.
authors.forename: Martine A
authors.initials: MA
authors.lastname: Collart
mesh_terms: D056890:Eukaryota / Q000201:enzymology* / Q000235:genetics*; D005786:Gene Expression Regulation; D009097:Multienzyme Complexes / Q000378:metabolism*; D012260:Ribonucleases / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D009097:Multienzyme Complexes; D015534:Trans-Activators; D012260:Ribonucleases
references.citation: Protein Cell. 2011 Sep;2(9):755-63
references.pmid: 21976065
references.citation: RNA. 2015 Apr;21(4):519-24
references.pmid: 25780122
references.citation: Cold Spring Harb Perspect Biol. 2012 Sep 01;4(9):a012286
references.pmid: 22763747
references.citation: Front Genet. 2013 Dec 20;4:302
references.pmid: 24391665
references.citation: Bioessays. 2000 Apr;22(4):327-36
references.pmid: 10723030
references.citation: PLoS One. 2009 Aug 25;4(8):e6760
references.pmid: 19707589
references.citation: J Cell Physiol. 2010 Jan;222(1):66-72
references.pmid: 19746446
references.citation: J Biol Chem. 2004 Mar 19;279(12):10848-54
references.pmid: 14707134
references.citation: Mol Cell Biol. 2002 Oct;22(19):6735-49
references.pmid: 12215531
references.citation: Front Genet. 2014 May 16;5:137
references.pmid: 24904637
references.citation: Genes Dev. 2009 Apr 15;23 (8):951-62
references.pmid: 19346402
references.citation: Nucleic Acids Res. 2000 Feb 1;28(3):809-17
references.pmid: 10637334
references.citation: Genetics. 2008 May;179(1):277-89
references.pmid: 18493053
references.citation: Crit Rev Biochem Mol Biol. 2012 Jul-Aug;47(4):315-33
references.pmid: 22416820
references.citation: Cell. 2001 Feb 9;104(3):377-86
references.pmid: 11239395
references.citation: Mol Cell. 2011 Feb 18;41(4):480-92
references.pmid: 21329885
references.citation: Biochem J. 1998 Dec 1;336 ( Pt 2):471-81
references.pmid: 9820826
references.citation: Cell Signal. 2013 Apr;25(4):743-51
references.pmid: 23280189
references.citation: Front Genet. 2014 May 26;5:143
references.pmid: 24904643
references.citation: J Biol Chem. 2006 Oct 20;281(42):31389-98
references.pmid: 16926149
references.citation: Structure. 2015 May 5;23 (5):921-8
references.pmid: 25914052
references.citation: J Biol Chem. 2010 Sep 10;285(37):28506-13
references.pmid: 20634287
references.citation: PLoS Genet. 2009 Feb;5(2):e1000364
references.pmid: 19197357
references.citation: Front Genet. 2013 Dec 23;4:296
references.pmid: 24391663
references.citation: Gene. 2003 Aug 14;313:1-16
references.pmid: 12957374
references.citation: RNA. 2011 Oct;17 (10 ):1788-94
references.pmid: 21862638
references.citation: EMBO J. 1998 Nov 16;17(22):6714-22
references.pmid: 9822614
references.citation: Front Genet. 2014 Aug 21;5:286
references.pmid: 25191340
references.citation: RNA. 2015 Jul;21(7):1335-45
references.pmid: 26015597
references.citation: Biochem Soc Trans. 2012 Aug;40(4):896-901
references.pmid: 22817755
references.citation: Gene. 1998 Jan 19;207(1):61-9
references.pmid: 9511744
references.citation: J Cell Sci. 2003 Jul 15;116(Pt 14):2929-36
references.pmid: 12771185
references.citation: RNA Biol. 2013 Feb;10(2):228-44
references.pmid: 23303381
references.citation: Genes Dev. 2011 Mar 15;25(6):581-93
references.pmid: 21406554
references.citation: Nat Struct Mol Biol. 2013 Nov;20(11):1281-8
references.pmid: 24121231
references.citation: PLoS One. 2014 Jan 17;9(1):e86218
references.pmid: 24465968
references.citation: Genetics. 1984 Dec;108(4):833-44
references.pmid: 6392016
references.citation: Biochem Soc Trans. 2015 Dec;43(6):1253-8
references.pmid: 26614669
references.citation: Cell. 2005 Sep 23;122(6):875-86
references.pmid: 16179257
references.citation: Prog Nucleic Acid Res Mol Biol. 2003;73:221-50
references.pmid: 12882519
references.citation: RNA Biol. 2012 Feb;9(2):148-54
references.pmid: 22418846
references.citation: Proc Natl Acad Sci U S A. 2007 Apr 3;104(14 ):5836-41
references.pmid: 17389396
references.citation: Biochim Biophys Acta. 2013 Jan;1829(1):127-33
references.pmid: 22975735
references.citation: EMBO J. 2006 Jul 12;25(13):3089-99
references.pmid: 16778766
references.citation: FEBS Lett. 2011 Jul 21;585(14):2182-6
references.pmid: 21669201
references.citation: Nature. 2010 Sep 23;467(7314):470-3
references.pmid: 20835226
references.citation: RNA. 2010 Jul;16(7):1356-70
references.pmid: 20504953
references.citation: ISRN Mol Biol. 2013 Jan 21;2013:548359
references.pmid: 27335678
references.citation: J Biol Chem. 2014 Nov 28;289(48):33125-30
references.pmid: 25315781
references.citation: EMBO J. 2005 Mar 9;24(5):1033-45
references.pmid: 15706350
references.citation: Genes Dev. 2009 Apr 1;23(7):837-48
references.pmid: 19339689
references.citation: Front Genet. 2014 May 20;5:135
references.pmid: 24904636
references.citation: Genes Dev. 2007 Dec 1;21(23):3135-48
references.pmid: 18056425
references.citation: PLoS Genet. 2014 Oct 23;10(10):e1004569
references.pmid: 25340856
references.citation: Prog Nucleic Acid Res Mol Biol. 2004;77:289-322
references.pmid: 15196896
references.citation: Mol Cell Biol. 2005 Jan;25(1):488-98
references.pmid: 15601868
references.citation: Genes Dev. 2013 Oct 1;27(19):2125-38
references.pmid: 24115769
references.citation: Mol Cell Biol. 2002 Dec;22(23):8254-66
references.pmid: 12417728
references.citation: Genes Dev. 2014 Apr 15;28(8):888-901
references.pmid: 24736845
references.citation: Genetics. 2007 Sep;177(1):123-35
references.pmid: 17660549
references.citation: PLoS One. 2011 Mar 28;6(3):e18302
references.pmid: 21464899
references.citation: Mol Cell. 2014 Jun 5;54(5):737-50
references.pmid: 24768540
references.citation: J Biol Chem. 2009 Apr 17;284(16):10343-52
references.pmid: 19204001
references.citation: Mol Microbiol. 2012 Feb;83(3):640-53
references.pmid: 22243599
references.citation: Nature. 2009 Sep 10;461(7261):225-9
references.pmid: 19701183
references.citation: Nat Struct Mol Biol. 2013 Jun;20(6):735-9
references.pmid: 23644599
references.citation: J Biol Chem. 2012 Aug 3;287(32):26796-805
references.pmid: 22707721
references.citation: Nucleic Acids Res. 2007;35(7):2428-39
references.pmid: 17392337
references.citation: Mol Cell. 2014 Jun 5;54(5):751-65
references.pmid: 24768538
references.citation: Mol Cell Biol. 2011 Apr;31(8):1610-23
references.pmid: 21321079
references.citation: Mol Cell Biol. 1995 Jul;15(7):3487-95
references.pmid: 7791755
references.citation: J Mol Biol. 2001 Dec 7;314(4):683-94
references.pmid: 11733989
references.citation: Mol Biol Cell. 2007 Jun;18(6):2274-87
references.pmid: 17429074
references.citation: RNA Biol. 2014;11(4):320-3
references.pmid: 24646520
references.citation: PLoS One. 2012;7(12):e51331
references.pmid: 23236473
references.citation: J Biol Chem. 2002 Jan 25;277(4):2835-42
references.pmid: 11696541
references.citation: Cell Rep. 2015 Oct 27;13(4):703-11
references.pmid: 26489469
references.citation: RNA. 2014 Sep;20(9):1398-409
references.pmid: 25035296
references.citation: J Biol Chem. 2006 Sep 1;281(35):25124-33
references.pmid: 16793774
references.citation: Genetics. 2001 Jun;158(2):627-34
references.pmid: 11404327
references.citation: Biochim Biophys Acta. 2013 Jun-Jul;1829(6-7):561-70
references.pmid: 23337855
references.citation: Mol Genet Genomics. 2008 Apr;279(4):323-37
references.pmid: 18214544
references.citation: Cell Rep. 2015 Jun 9;11(9):1425-36
references.pmid: 26027925
references.citation: Wiley Interdiscip Rev RNA. 2014 Nov-Dec;5(6):883-901
references.pmid: 25044499
references.citation: PLoS One. 2015 May 01;10(5):e0125599
references.pmid: 25933433
references.citation: Gene. 2012 Jan 15;492(1):42-53
references.pmid: 22027279
references.citation: PLoS Biol. 2012;10(6):e1001342
references.pmid: 22719226
references.citation: EMBO J. 2015 Jul 14;34(14 ):1905-24
references.pmid: 25971775
references.citation: J Biol Chem. 2007 May 25;282(21):15430-8
references.pmid: 17389596
references.citation: Mol Cell Biol. 2015 Jun 1;35(11):1915-25
references.pmid: 25776559
references.citation: EMBO J. 1993 Jan;12(1):177-86
references.pmid: 8428577
references.citation: J Mol Biol. 2000 Oct 20;303(2):131-43
references.pmid: 11023781
references.citation: Genes Dev. 2005 Dec 15;19(24):3004-16
references.pmid: 16357218
references.citation: Biochemistry. 2004 Jun 29;43(25):8152-9
references.pmid: 15209511
references.citation: PLoS Genet. 2012;8(11):e1003040
references.pmid: 23144630
references.citation: Front Genet. 2014 May 19;5:141
references.pmid: 24904641
references.citation: Mol Cell Biol. 2003 Apr;23(8):2800-20
references.pmid: 12665580
references.citation: Genes Dev. 1994 Mar 1;8(5):525-37
references.pmid: 7926748