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.

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