LOTUS domain protein MARF1 binds CCR4-NOT deadenylase complex to post-transcriptionally regulate gene expression in oocytes

Nat Commun. 2018 Oct 2;9(1):4031. doi: 10.1038/s41467-018-06404-w.

Abstract

Post-transcriptional regulation of gene expression plays an essential role during oocyte maturation. Here we report that Drosophila MARF1 (Meiosis Regulator And mRNA Stability Factor 1), which consists of one RNA-recognition motif and six tandem LOTUS domains with unknown molecular function, is essential for oocyte maturation. When tethered to a reporter mRNA, MARF1 post-transcriptionally silences reporter expression by shortening reporter mRNA poly-A tail length and thereby reducing reporter protein level. This activity is mediated by the MARF1 LOTUS domain, which binds the CCR4-NOT deadenylase complex. MARF1 binds cyclin A mRNA and shortens its poly-A tail to reduce Cyclin A protein level during oocyte maturation. This study identifies MARF1 as a regulator in oocyte maturation and defines the conserved LOTUS domain as a post-transcriptional effector domain that recruits CCR4-NOT deadenylase complex to shorten target mRNA poly-A tails and suppress their translation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cyclin A / metabolism*
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Female
  • Fertility
  • Male
  • Meiosis
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Oocytes / metabolism*
  • Protein Transport
  • RNA 3' End Processing*
  • Ribonucleases / metabolism*

Substances

  • Cyclin A
  • Drosophila Proteins
  • Marf protein, Drosophila
  • Membrane Proteins
  • CCR4 protein, Drosophila
  • Ribonucleases