CDK12 globally stimulates RNA polymerase II transcription elongation and carboxyl-terminal domain phosphorylation.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
20 08 2020
20 08 2020
Historique:
accepted:
04
06
2020
revised:
02
06
2020
received:
07
04
2020
entrez:
18
8
2020
pubmed:
18
8
2020
medline:
25
9
2020
Statut:
ppublish
Résumé
Cyclin-dependent kinase 12 (CDK12) phosphorylates the carboxyl-terminal domain (CTD) of RNA polymerase II (pol II) but its roles in transcription beyond the expression of DNA damage response genes remain unclear. Here, we have used TT-seq and mNET-seq to monitor the direct effects of rapid CDK12 inhibition on transcription activity and CTD phosphorylation in human cells. CDK12 inhibition causes a genome-wide defect in transcription elongation and a global reduction of CTD Ser2 and Ser5 phosphorylation. The elongation defect is explained by the loss of the elongation factors LEO1 and CDC73, part of PAF1 complex, and SPT6 from the newly-elongating pol II. Our results indicate that CDK12 is a general activator of pol II transcription elongation and indicate that it targets both Ser2 and Ser5 residues of the pol II CTD.
Identifiants
pubmed: 32805052
pii: 5858455
doi: 10.1093/nar/gkaa514
pmc: PMC7641311
doi:
Substances chimiques
Chromatin
0
Transcriptional Elongation Factors
0
Serine
452VLY9402
RNA
63231-63-0
CDK12 protein, human
EC 2.7.11.22
Cyclin-Dependent Kinases
EC 2.7.11.22
RNA Polymerase II
EC 2.7.7.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7712-7727Subventions
Organisme : Wellcome Trust
ID : WT210641/Z/18/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0400653
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 210641/Z/18/Z
Pays : United Kingdom
Organisme : European Research Council
ID : 693023
Pays : International
Organisme : Wellcome Trust
ID : WT106134AIA
Pays : United Kingdom
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
Références
Mol Cell. 1999 Mar;3(3):405-11
pubmed: 10198643
EMBO Rep. 2019 Sep;20(9):e47592
pubmed: 31347271
Nature. 2011 Jun 29;474(7353):609-15
pubmed: 21720365
Mol Cell Biol. 2012 Nov;32(22):4691-704
pubmed: 22988298
Mol Cell. 2018 Dec 20;72(6):970-984.e7
pubmed: 30449723
Nat Struct Mol Biol. 2015 May;22(5):396-403
pubmed: 25849141
Genes Dev. 2019 Apr 1;33(7-8):418-435
pubmed: 30819820
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Mol Cell Biol. 2015 Jan;35(2):468-78
pubmed: 25384976
Nat Commun. 2019 Apr 15;10(1):1757
pubmed: 30988284
Development. 2013 Sep;140(17):3703-13
pubmed: 23903194
Genes Dev. 2001 Dec 15;15(24):3319-29
pubmed: 11751637
Nat Commun. 2018 Feb 7;9(1):543
pubmed: 29416031
J Biol Chem. 2015 Jan 16;290(3):1786-95
pubmed: 25429106
J Biol Chem. 1995 May 26;270(21):12335-8
pubmed: 7759473
Nat Chem Biol. 2016 Oct;12(10):876-84
pubmed: 27571479
Nat Rev Mol Cell Biol. 2015 Mar;16(3):167-77
pubmed: 25693130
Genes Dev. 2011 Oct 15;25(20):2158-72
pubmed: 22012619
RNA Biol. 2016;13(3):265-71
pubmed: 26853452
Nat Commun. 2014 Mar 24;5:3505
pubmed: 24662513
Nucleic Acids Res. 2015 Mar 11;43(5):2575-89
pubmed: 25712099
Nature. 2018 Dec;564(7734):141-145
pubmed: 30487607
Nat Struct Mol Biol. 2016 Sep 6;23(9):771-7
pubmed: 27605205
Cell Death Differ. 2016 Jun;23(6):1038-48
pubmed: 26658019
Science. 2015 Dec 11;350(6266):1383-6
pubmed: 26659056
Methods Enzymol. 2014;548:189-213
pubmed: 25399647
Nat Protoc. 2016 Mar;11(3):413-28
pubmed: 26844429
Cell. 2015 Apr 23;161(3):526-540
pubmed: 25910207
Biochim Biophys Acta. 2013 Jan;1829(1):55-62
pubmed: 22982363
Biochim Biophys Acta. 2015 Sep;1849(9):1179-87
pubmed: 26189575
Nucleic Acids Res. 2017 Jun 20;45(11):6698-6716
pubmed: 28334900
Science. 2007 Dec 14;318(5857):1780-2
pubmed: 18079404
Genome Biol. 2010;11(10):R106
pubmed: 20979621
Science. 2016 Jun 3;352(6290):1225-8
pubmed: 27257258
RNA. 2008 Sep;14(9):1959-72
pubmed: 18658122
Nature. 2018 Aug;560(7720):607-612
pubmed: 30135578
Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):755-60
pubmed: 19136632
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W187-91
pubmed: 24799436
Genes Dev. 2010 Oct 15;24(20):2303-16
pubmed: 20952539
Curr Protoc Mol Biol. 2004 May;Chapter 18:Unit 18.11
pubmed: 18265343
J Biol Chem. 2014 Mar 28;289(13):9247-53
pubmed: 24554720
Elife. 2017 Oct 10;6:
pubmed: 28994650
PLoS Genet. 2016 Jan 14;12(1):e1005794
pubmed: 26765774
Mol Cell Biol. 2015 Mar;35(6):928-38
pubmed: 25561469
Mol Cell. 2016 Jan 21;61(2):305-14
pubmed: 26799765
Genes Dev. 2014 Feb 15;28(4):342-56
pubmed: 24478330
Transcription. 2015;6(5):79-90
pubmed: 26399478
Elife. 2014 Apr 29;3:e02407
pubmed: 24843027