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

Tamiko Nishimura1, Hana Fakim1, Tobias Brandmann2

  • 1Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.

Nucleic Acids Research
|October 27, 2018
PubMed

Insights

Meiosis arrest female 1 (MARF1) protein silences gene expression by cutting targeted messenger RNAs (mRNAs). It also recruits the DCP1:DCP2 decapping complex, revealing MARF1’s dual role in post-transcriptional gene silencing.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • RNA Biology

Background:

  • Meiosis arrest female 1 (MARF1) is crucial for mouse oocyte meiotic progression and retrotransposon control.
  • MARF1 expression extends to somatic cells, but its functional mechanism remains largely unelucidated.
  • Human MARF1 possesses distinct domains: a NYN-like domain, two RNA Recognition Motifs (RRMs), and eight LOTUS domains.

Purpose of the Study:

  • To investigate the mechanism of action of MARF1 in somatic cells.
  • To elucidate how MARF1 contributes to post-transcriptional gene silencing.
  • To characterize the enzymatic activity and structural features of human MARF1.

Main Methods:

  • Biochemical assays to assess MARF1 interactions with mRNA processing complexes.
  • Crystallography to determine the structure of the human MARF1 NYN domain.
  • Functional studies to evaluate the role of MARF1's endoribonuclease activity in gene repression.

Main Results:

  • MARF1 directly silences targeted mRNAs through post-transcriptional mechanisms.
  • MARF1 physically associates with the DCP1:DCP2 mRNA decapping complex.
  • The NYN domain of MARF1 exhibits bona fide endoribonuclease activity, essential for mRNA repression.

Conclusions:

  • MARF1 acts as an endoribonuclease to repress targeted mRNAs.
  • MARF1 functions as a scaffold, recruiting the DCP1:DCP2 decapping complex to specific mRNAs.
  • This dual mechanism underscores MARF1's role in post-transcriptional gene silencing.

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