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DEAD-box helicase eIF4A2 inhibits CNOT7 deadenylation activity

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 co...

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Autores principales: Meijer, Hedda A, Schmidt, Tobias, Gillen, Sarah L, Langlais, Claudia, Jukes-Jones, Rebekah, de Moor, Cornelia H, Cain, Kelvin, Wilczynska, Ania, Bushell, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736043/
https://www.ncbi.nlm.nih.gov/pubmed/31180491
http://dx.doi.org/10.1093/nar/gkz509
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author Meijer, Hedda A
Schmidt, Tobias
Gillen, Sarah L
Langlais, Claudia
Jukes-Jones, Rebekah
de Moor, Cornelia H
Cain, Kelvin
Wilczynska, Ania
Bushell, Martin
author_facet Meijer, Hedda A
Schmidt, Tobias
Gillen, Sarah L
Langlais, Claudia
Jukes-Jones, Rebekah
de Moor, Cornelia H
Cain, Kelvin
Wilczynska, Ania
Bushell, Martin
author_sort Meijer, Hedda A
collection PubMed
description 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.
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spelling pubmed-67360432019-09-16 DEAD-box helicase eIF4A2 inhibits CNOT7 deadenylation activity Meijer, Hedda A Schmidt, Tobias Gillen, Sarah L Langlais, Claudia Jukes-Jones, Rebekah de Moor, Cornelia H Cain, Kelvin Wilczynska, Ania Bushell, Martin Nucleic Acids Res RNA and RNA-protein complexes 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. Oxford University Press 2019-09-05 2019-06-10 /pmc/articles/PMC6736043/ /pubmed/31180491 http://dx.doi.org/10.1093/nar/gkz509 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle RNA and RNA-protein complexes
Meijer, Hedda A
Schmidt, Tobias
Gillen, Sarah L
Langlais, Claudia
Jukes-Jones, Rebekah
de Moor, Cornelia H
Cain, Kelvin
Wilczynska, Ania
Bushell, Martin
DEAD-box helicase eIF4A2 inhibits CNOT7 deadenylation activity
title DEAD-box helicase eIF4A2 inhibits CNOT7 deadenylation activity
title_full DEAD-box helicase eIF4A2 inhibits CNOT7 deadenylation activity
title_fullStr DEAD-box helicase eIF4A2 inhibits CNOT7 deadenylation activity
title_full_unstemmed DEAD-box helicase eIF4A2 inhibits CNOT7 deadenylation activity
title_short DEAD-box helicase eIF4A2 inhibits CNOT7 deadenylation activity
title_sort dead-box helicase eif4a2 inhibits cnot7 deadenylation activity
topic RNA and RNA-protein complexes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736043/
https://www.ncbi.nlm.nih.gov/pubmed/31180491
http://dx.doi.org/10.1093/nar/gkz509
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