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

ELife
William R BrothersMarc R Fabian

Abstract

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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Citations

Oct 25, 2020·Biological Chemistry·Jana KubíkováMandy Jeske
Feb 6, 2021·Biological Chemistry·Jana KubíkováMandy Jeske
Mar 5, 2021·The FEBS Journal·Fivos Borbolis, Popi Syntichaki

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Methods Mentioned

BETA
iCLIP
immunoprecipitation
immunoprecipitations
PCR
genetrap
transfection
CLIP
transfections
Hi-Seq2500
Assay

Software Mentioned

Trimmomatic
macs2
Picard
Fiji
Integrative Genomic Viewer ( IGV )
STAR
samtools
Homer
Phyre2

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