DEAD-box helicase eIF4A2 inhibits CNOT7 deadenylation activity.
Binding Sites
/ genetics
Binding, Competitive
DEAD-box RNA Helicases
/ chemistry
Exoribonucleases
/ genetics
HEK293 Cells
HeLa Cells
Humans
Models, Genetic
Protein Binding
Protein Domains
Proto-Oncogene Proteins
/ chemistry
RNA, Messenger
/ genetics
Repressor Proteins
/ genetics
Telomeric Repeat Binding Protein 1
/ genetics
Transcription Factors
/ genetics
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
05 09 2019
05 09 2019
Historique:
accepted:
05
06
2019
revised:
26
05
2019
received:
22
11
2018
pubmed:
11
6
2019
medline:
18
12
2019
entrez:
11
6
2019
Statut:
ppublish
Résumé
The CCR4-NOT complex plays an important role in the translational repression and deadenylation of mRNAs. However, little is known about the specific roles of interacting factors. We demonstrate that the DEAD-box helicases eIF4A2 and DDX6 interact directly with the MA3 and MIF domains of CNOT1 and compete for binding. Furthermore, we now show that incorporation of eIF4A2 into the CCR4-NOT complex inhibits CNOT7 deadenylation activity in contrast to DDX6 which enhances CNOT7 activity. Polyadenylation tests (PAT) on endogenous mRNAs determined that eIF4A2 bound mRNAs have longer poly(A) tails than DDX6 bound mRNAs. Immunoprecipitation experiments show that eIF4A2 does not inhibit CNOT7 association with the CCR4-NOT complex but instead inhibits CNOT7 activity. We identified a CCR4-NOT interacting factor, TAB182, that modulates helicase recruitment into the CCR4-NOT complex, potentially affecting the outcome for the targeted mRNA. Together, these data show that the fate of an mRNA is dependent on the specific recruitment of either eIF4A2 or DDX6 to the CCR4-NOT complex which results in different pathways for translational repression and mRNA deadenylation.
Identifiants
pubmed: 31180491
pii: 5513320
doi: 10.1093/nar/gkz509
pmc: PMC6736043
doi:
Substances chimiques
CNOT1 protein, human
0
Proto-Oncogene Proteins
0
RNA, Messenger
0
Repressor Proteins
0
TNKS1BP1 protein, human
0
Telomeric Repeat Binding Protein 1
0
Transcription Factors
0
CNOT7 protein, human
EC 3.1.-
Exoribonucleases
EC 3.1.-
DDX6 protein, human
EC 3.6.1.-
DEAD-box RNA Helicases
EC 3.6.4.13
EIF4A2 protein, human
EC 3.6.4.13
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8224-8238Subventions
Organisme : Medical Research Council
ID : MC_EX_G0902052
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UP_A600_1024
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00025/6
Pays : United Kingdom
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
Références
Biochem J. 2009 Aug 27;422(3):443-53
pubmed: 19558367
Genome Biol. 2017 Oct 31;18(1):211
pubmed: 29089021
Science. 2013 Apr 5;340(6128):82-5
pubmed: 23559250
RNA. 2004 Oct;10(10):1518-25
pubmed: 15337849
Biochem J. 2015 Jul 1;469(1):169-76
pubmed: 25944446
EMBO J. 2016 Jun 1;35(11):1186-203
pubmed: 27009120
Mol Cell. 2014 Oct 2;56(1):67-78
pubmed: 25280104
Nat Methods. 2013 Dec;10(12):1239-45
pubmed: 24162924
Bioessays. 2016 Oct;38(10):1048-58
pubmed: 27502453
Cell Death Differ. 2015 Jun;22(6):890-7
pubmed: 25941166
Biochem Soc Trans. 2015 Dec;43(6):1227-33
pubmed: 26614665
RNA. 2015 Oct;21(10):1826-33
pubmed: 26286746
RNA. 2014 Sep;20(9):1398-409
pubmed: 25035296
Elife. 2018 Jul 25;7:
pubmed: 30044225
EMBO J. 1992 Jul;11(7):2643-54
pubmed: 1378397
Nature. 2017 Mar 23;543(7646):568-572
pubmed: 28297718
Oncotarget. 2015 Mar 30;6(9):7011-22
pubmed: 25749521
Cell Rep. 2016 Nov 15;17(8):1978-1989
pubmed: 27851962
Biochem J. 2018 Nov 9;475(21):3437-3450
pubmed: 30309886
Mol Cell. 2018 Jun 21;70(6):1081-1088.e5
pubmed: 29932901
Gene. 1998 Aug 17;216(1):1-11
pubmed: 9714706
Nat Commun. 2016 Aug 25;7:12626
pubmed: 27558897
Mol Cell. 2009 Sep 24;35(6):868-80
pubmed: 19716330
RNA. 2008 Dec;14(12):2580-96
pubmed: 18978028
Mol Cell. 2014 Jun 5;54(5):751-65
pubmed: 24768538
Nucleic Acids Res. 2012 Nov;40(21):11058-72
pubmed: 22977175
Nat Commun. 2018 Aug 3;9(1):3068
pubmed: 30076308
Nucleic Acids Res. 2016 Jul 8;44(12):5924-35
pubmed: 27095199
Cancer Res. 2017 May 1;77(9):2328-2338
pubmed: 28202517
Nucleic Acids Res. 2016 Jul 27;44(13):6318-34
pubmed: 27342281
Cell Rep. 2015 Jun 9;11(9):1425-36
pubmed: 26027925
Mol Cell Biol. 1997 Dec;17(12):6940-7
pubmed: 9372926
Mol Cell. 2011 Oct 7;44(1):120-33
pubmed: 21981923
PLoS One. 2016 Mar 02;11(3):e0150239
pubmed: 26934103
Mol Cell. 2018 Jun 21;70(6):1089-1100.e8
pubmed: 29932902
Mol Cell. 2016 May 5;62(3):462-471
pubmed: 27153541
Mol Cell. 2014 Oct 2;56(1):79-89
pubmed: 25280105
Wiley Interdiscip Rev RNA. 2016 Jul;7(4):438-54
pubmed: 26821858
Biochem Soc Trans. 2014 Aug;42(4):1229-37
pubmed: 25110030
Cell. 2012 Jun 8;149(6):1393-406
pubmed: 22658674
Genes Dev. 2002 Nov 15;16(22):2906-22
pubmed: 12435632
Nucleic Acids Res. 2018 Jul 6;46(12):6330-6343
pubmed: 29669014
Mol Cell. 2014 Jun 5;54(5):737-50
pubmed: 24768540
Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):8866-71
pubmed: 18579786
Cell Rep. 2015 Oct 27;13(4):703-711
pubmed: 26489469
RNA. 2009 Jan;15(1):21-32
pubmed: 19029310