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A non-canonical role for the EDC4 decapping factor in regulating MARF1-mediated mRNA decay

EDC4 is a core component of processing (P)-bodies that binds the DCP2 decapping enzyme and stimulates mRNA decay. EDC4 also interacts with mammalian MARF1, a recently identified endoribonuclease that promotes oogenesis and contains a number of RNA binding domains, including two RRMs and multiple LOT...

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Detalles Bibliográficos
Autores principales: Brothers, William R, Hebert, Steven, Kleinman, Claudia L, Fabian, Marc R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279887/
https://www.ncbi.nlm.nih.gov/pubmed/32510323
http://dx.doi.org/10.7554/eLife.54995
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author Brothers, William R
Hebert, Steven
Kleinman, Claudia L
Fabian, Marc R
author_facet Brothers, William R
Hebert, Steven
Kleinman, Claudia L
Fabian, Marc R
author_sort Brothers, William R
collection PubMed
description EDC4 is a core component of processing (P)-bodies that binds the DCP2 decapping enzyme and stimulates mRNA decay. EDC4 also interacts with mammalian MARF1, a recently identified endoribonuclease that promotes oogenesis and contains a number of RNA binding domains, including two RRMs and multiple LOTUS domains. How EDC4 regulates MARF1 action and the identity of MARF1 target mRNAs is not known. Our transcriptome-wide analysis identifies bona fide MARF1 target mRNAs and indicates that MARF1 predominantly binds their 3’ UTRs via its LOTUS domains to promote their decay. We also show that a MARF1 RRM plays an essential role in enhancing its endonuclease activity. Importantly, we establish that EDC4 impairs MARF1 activity by preventing its LOTUS domains from binding target mRNAs. Thus, EDC4 not only serves as an enhancer of mRNA turnover that binds DCP2, but also as a repressor that binds MARF1 to prevent the decay of MARF1 target mRNAs.
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spelling pubmed-72798872020-06-10 A non-canonical role for the EDC4 decapping factor in regulating MARF1-mediated mRNA decay Brothers, William R Hebert, Steven Kleinman, Claudia L Fabian, Marc R eLife Chromosomes and Gene Expression EDC4 is a core component of processing (P)-bodies that binds the DCP2 decapping enzyme and stimulates mRNA decay. EDC4 also interacts with mammalian MARF1, a recently identified endoribonuclease that promotes oogenesis and contains a number of RNA binding domains, including two RRMs and multiple LOTUS domains. How EDC4 regulates MARF1 action and the identity of MARF1 target mRNAs is not known. Our transcriptome-wide analysis identifies bona fide MARF1 target mRNAs and indicates that MARF1 predominantly binds their 3’ UTRs via its LOTUS domains to promote their decay. We also show that a MARF1 RRM plays an essential role in enhancing its endonuclease activity. Importantly, we establish that EDC4 impairs MARF1 activity by preventing its LOTUS domains from binding target mRNAs. Thus, EDC4 not only serves as an enhancer of mRNA turnover that binds DCP2, but also as a repressor that binds MARF1 to prevent the decay of MARF1 target mRNAs. eLife Sciences Publications, Ltd 2020-06-08 /pmc/articles/PMC7279887/ /pubmed/32510323 http://dx.doi.org/10.7554/eLife.54995 Text en © 2020, Brothers et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Chromosomes and Gene Expression
Brothers, William R
Hebert, Steven
Kleinman, Claudia L
Fabian, Marc R
A non-canonical role for the EDC4 decapping factor in regulating MARF1-mediated mRNA decay
title A non-canonical role for the EDC4 decapping factor in regulating MARF1-mediated mRNA decay
title_full A non-canonical role for the EDC4 decapping factor in regulating MARF1-mediated mRNA decay
title_fullStr A non-canonical role for the EDC4 decapping factor in regulating MARF1-mediated mRNA decay
title_full_unstemmed A non-canonical role for the EDC4 decapping factor in regulating MARF1-mediated mRNA decay
title_short A non-canonical role for the EDC4 decapping factor in regulating MARF1-mediated mRNA decay
title_sort non-canonical role for the edc4 decapping factor in regulating marf1-mediated mrna decay
topic Chromosomes and Gene Expression
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279887/
https://www.ncbi.nlm.nih.gov/pubmed/32510323
http://dx.doi.org/10.7554/eLife.54995
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