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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Bibliographic Details
Published ineLife Vol. 9
Main Authors Brothers, William R, Hebert, Steven, Kleinman, Claudia L, Fabian, Marc R
Format Journal Article
LanguageEnglish
Published England eLife Sciences Publications Ltd 08.06.2020
eLife Sciences Publications, Ltd
Subjects
Animals
Cell Cycle Proteins - chemistry
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Chromosomes and Gene Expression
Endonuclease
Endoribonucleases - chemistry
Endoribonucleases - genetics
Endoribonucleases - metabolism
Experiments
Gene expression
HEK293 Cells
Humans
mRNA decapping
mRNA decay
mRNA turnover
Oogenesis
Proteins
Proteins - chemistry
Proteins - genetics
Proteins - metabolism
RNA binding protein
RNA Caps - metabolism
RNA Stability - genetics
RNA, Messenger - chemistry
RNA, Messenger - genetics
RNA, Messenger - metabolism
Transcriptome - genetics
endonuclease
RNA binding protein
chromosomes
none
mRNA decapping
gene expression
mRNA decay
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Summary: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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ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.54995