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The cAMP pathway regulates mRNA decay through phosphorylation of the RNA-binding protein TIS11b/BRF1

TPA-inducible sequence 11b/butyrate response factor 1 (TIS11b/BRF1) belongs to the tristetraprolin (TTP) family of zinc-finger proteins, which bind to mRNAs containing AU-rich elements in their 3′-untranslated region and target them for degradation. Regulation of TTP family function through phosphor...

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Autores principales: Rataj, Felicitas, Planel, Séverine, Desroches-Castan, Agnès, Le Douce, Juliette, Lamribet, Khadija, Denis, Josiane, Feige, Jean-Jacques, Cherradi, Nadia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5170607/
https://www.ncbi.nlm.nih.gov/pubmed/27708140
http://dx.doi.org/10.1091/mbc.E16-06-0379
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author Rataj, Felicitas
Planel, Séverine
Desroches-Castan, Agnès
Le Douce, Juliette
Lamribet, Khadija
Denis, Josiane
Feige, Jean-Jacques
Cherradi, Nadia
author_facet Rataj, Felicitas
Planel, Séverine
Desroches-Castan, Agnès
Le Douce, Juliette
Lamribet, Khadija
Denis, Josiane
Feige, Jean-Jacques
Cherradi, Nadia
author_sort Rataj, Felicitas
collection PubMed
description TPA-inducible sequence 11b/butyrate response factor 1 (TIS11b/BRF1) belongs to the tristetraprolin (TTP) family of zinc-finger proteins, which bind to mRNAs containing AU-rich elements in their 3′-untranslated region and target them for degradation. Regulation of TTP family function through phosphorylation by p38 MAP kinase and Akt/protein kinase B signaling pathways has been extensively studied. In contrast, the role of cAMP-dependent protein kinase (PKA) in the control of TTP family activity in mRNA decay remains largely unknown. Here we show that PKA activation induces TIS11b gene expression and protein phosphorylation. Site-directed mutagenesis combined with kinase assays and specific phosphosite immunodetection identified Ser-54 (S54) and Ser-334 (S334) as PKA target amino acids in vitro and in vivo. Phosphomimetic mutation of the C-terminal S334 markedly increased TIS11b half-life and, unexpectedly, enhanced TIS11b activity on mRNA decay. Examination of protein–protein interactions between TIS11b and components of the mRNA decay machinery revealed that mimicking phosphorylation at S334 enhances TIS11b interaction with the decapping coactivator Dcp1a, while preventing phosphorylation at S334 potentiates its interaction with the Ccr4-Not deadenylase complex subunit Cnot1. Collectively our findings establish for the first time that cAMP-elicited phosphorylation of TIS11b plays a key regulatory role in its mRNA decay-promoting function.
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spelling pubmed-51706072017-02-16 The cAMP pathway regulates mRNA decay through phosphorylation of the RNA-binding protein TIS11b/BRF1 Rataj, Felicitas Planel, Séverine Desroches-Castan, Agnès Le Douce, Juliette Lamribet, Khadija Denis, Josiane Feige, Jean-Jacques Cherradi, Nadia Mol Biol Cell Articles TPA-inducible sequence 11b/butyrate response factor 1 (TIS11b/BRF1) belongs to the tristetraprolin (TTP) family of zinc-finger proteins, which bind to mRNAs containing AU-rich elements in their 3′-untranslated region and target them for degradation. Regulation of TTP family function through phosphorylation by p38 MAP kinase and Akt/protein kinase B signaling pathways has been extensively studied. In contrast, the role of cAMP-dependent protein kinase (PKA) in the control of TTP family activity in mRNA decay remains largely unknown. Here we show that PKA activation induces TIS11b gene expression and protein phosphorylation. Site-directed mutagenesis combined with kinase assays and specific phosphosite immunodetection identified Ser-54 (S54) and Ser-334 (S334) as PKA target amino acids in vitro and in vivo. Phosphomimetic mutation of the C-terminal S334 markedly increased TIS11b half-life and, unexpectedly, enhanced TIS11b activity on mRNA decay. Examination of protein–protein interactions between TIS11b and components of the mRNA decay machinery revealed that mimicking phosphorylation at S334 enhances TIS11b interaction with the decapping coactivator Dcp1a, while preventing phosphorylation at S334 potentiates its interaction with the Ccr4-Not deadenylase complex subunit Cnot1. Collectively our findings establish for the first time that cAMP-elicited phosphorylation of TIS11b plays a key regulatory role in its mRNA decay-promoting function. The American Society for Cell Biology 2016-12-01 /pmc/articles/PMC5170607/ /pubmed/27708140 http://dx.doi.org/10.1091/mbc.E16-06-0379 Text en © 2016 Rataj, Planel, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Rataj, Felicitas
Planel, Séverine
Desroches-Castan, Agnès
Le Douce, Juliette
Lamribet, Khadija
Denis, Josiane
Feige, Jean-Jacques
Cherradi, Nadia
The cAMP pathway regulates mRNA decay through phosphorylation of the RNA-binding protein TIS11b/BRF1
title The cAMP pathway regulates mRNA decay through phosphorylation of the RNA-binding protein TIS11b/BRF1
title_full The cAMP pathway regulates mRNA decay through phosphorylation of the RNA-binding protein TIS11b/BRF1
title_fullStr The cAMP pathway regulates mRNA decay through phosphorylation of the RNA-binding protein TIS11b/BRF1
title_full_unstemmed The cAMP pathway regulates mRNA decay through phosphorylation of the RNA-binding protein TIS11b/BRF1
title_short The cAMP pathway regulates mRNA decay through phosphorylation of the RNA-binding protein TIS11b/BRF1
title_sort camp pathway regulates mrna decay through phosphorylation of the rna-binding protein tis11b/brf1
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5170607/
https://www.ncbi.nlm.nih.gov/pubmed/27708140
http://dx.doi.org/10.1091/mbc.E16-06-0379
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