Human MARF1 is an endoribonuclease that interacts with the DCP1:2 decapping complex and degrades target mRNAs

Tamiko Nishimura; Hana Fakim; Tobias Brandmann; Ji-Young Youn; Anne-Claude Gingras; Martin Jinek; Marc R Fabian

doi:10.1093/nar/gky1011

Human MARF1 is an endoribonuclease that interacts with the DCP1:2 decapping complex and degrades target mRNAs

Nucleic Acids Res. 2018 Dec 14;46(22):12008-12021. doi: 10.1093/nar/gky1011.

Authors

Tamiko Nishimura¹, Hana Fakim¹, Tobias Brandmann², Ji-Young Youn³, Anne-Claude Gingras^{3

4}, Martin Jinek², Marc R Fabian^{1

5}

Affiliations

¹ Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
² Department of Biochemistry, University of Zurich, Switzerland.
³ Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
⁴ Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
⁵ Department of Oncology, McGill University, Montreal, Quebec, Canada.

Abstract

Meiosis arrest female 1 (MARF1) is a cytoplasmic RNA binding protein that is essential for meiotic progression of mouse oocytes, in part by limiting retrotransposon expression. MARF1 is also expressed in somatic cells and tissues; however, its mechanism of action has yet to be investigated. Human MARF1 contains a NYN-like domain, two RRMs and eight LOTUS domains. Here we provide evidence that MARF1 post-transcriptionally silences targeted mRNAs. MARF1 physically interacts with the DCP1:DCP2 mRNA decapping complex but not with deadenylation machineries. Importantly, we provide a 1.7 Å resolution crystal structure of the human MARF1 NYN domain, which we demonstrate is a bona fide endoribonuclease, the activity of which is essential for the repression of MARF1-targeted mRNAs. Thus, MARF1 post-transcriptionally represses gene expression by serving as both an endoribonuclease and as a platform that recruits the DCP1:DCP2 decapping complex to targeted mRNAs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Binding Sites
Cell Cycle Proteins / chemistry
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism*
Crystallography, X-Ray
Endoribonucleases / chemistry
Endoribonucleases / genetics
Endoribonucleases / metabolism*
Escherichia coli / genetics
Escherichia coli / metabolism
Gene Expression
HEK293 Cells
HeLa Cells
Humans
Mice
Models, Molecular
Protein Binding
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
Protein Interaction Domains and Motifs
Protein Isoforms / chemistry
Protein Isoforms / genetics
Protein Isoforms / metabolism
RNA Cleavage
RNA Interference*
RNA, Messenger / chemistry
RNA, Messenger / genetics
RNA, Messenger / metabolism
Recombinant Proteins / chemistry
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Sequence Homology, Amino Acid
Trans-Activators / chemistry
Trans-Activators / genetics
Trans-Activators / metabolism*

Substances

Cell Cycle Proteins
MARF1 protein, mouse
Protein Isoforms
RNA, Messenger
Recombinant Proteins
Trans-Activators
Endoribonucleases
MARF1 protein, human
DCP1A protein, human
DCP2 protein, human

Grants and funding

MOP-130425/CIHR/Canada