The EDC4‐XRN1 interaction controls P‐body dynamics to link mRNA decapping with decay

Author:

Brothers William R1ORCID,Ali Farah1,Kajjo Sam1ORCID,Fabian Marc R123ORCID

Affiliation:

1. Lady Davis Institute for Medical Research Jewish General Hospital Montreal QC Canada

2. Department of Biochemistry McGill University Montreal QC Canada

3. Department of Oncology McGill University Montreal QC Canada

Abstract

AbstractDeadenylation‐dependent mRNA decapping and decay is the major cytoplasmic mRNA turnover pathway in eukaryotes. Many mRNA decapping and decay factors are associated with each other via protein–protein interaction motifs. For example, the decapping enzyme DCP2 and the 5'–3' exonuclease XRN1 interact with the enhancer of mRNA‐decapping protein 4 (EDC4), a large scaffold that has been reported to stimulate mRNA decapping. mRNA decapping and decay factors are also found in processing bodies (P‐bodies), evolutionarily conserved ribonucleoprotein granules that are often enriched with mRNAs targeted for decay, yet paradoxically are not required for mRNA decay to occur. Here, we show that disrupting the EDC4‐XRN1 interaction or altering their stoichiometry inhibits mRNA decapping, with microRNA‐targeted mRNAs being stabilized in a translationally repressed state. Importantly, we demonstrate that this concomitantly leads to larger P‐bodies that are responsible for preventing mRNA decapping. Finally, we demonstrate that P‐bodies support cell viability and prevent stress granule formation when XRN1 is limiting. Taken together, these data demonstrate that the interaction between XRN1 and EDC4 regulates P‐body dynamics to properly coordinate mRNA decapping with 5′–3′ decay in human cells.

Funder

Natural Sciences and Engineering Research Council of Canada

Publisher

Springer Science and Business Media LLC

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,Molecular Biology,General Neuroscience

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