ELAVL2-directed RNA regulatory network drives the formation of quiescent primordial follicles

EMBO Rep. 2019 Dec 5;20(12):e48251. doi: 10.15252/embr.201948251. Epub 2019 Oct 28.

Abstract

Formation of primordial follicles is a fundamental, early process in mammalian oogenesis. However, little is known about the underlying mechanisms. We herein report that the RNA-binding proteins ELAVL2 and DDX6 are indispensable for the formation of quiescent primordial follicles in mouse ovaries. We show that Elavl2 knockout females are infertile due to defective primordial follicle formation. ELAVL2 associates with mRNAs encoding components of P-bodies (cytoplasmic RNP granules involved in the decay and storage of RNA) and directs the assembly of P-body-like granules by promoting the translation of DDX6 in oocytes prior to the formation of primordial follicles. Deletion of Ddx6 disturbs the assembly of P-body-like granules and severely impairs the formation of primordial follicles, indicating the potential importance of P-body-like granules in the formation of primordial follicles. Furthermore, Ddx6-deficient oocytes are abnormally enlarged due to misregulated PI3K-AKT signaling. Our data reveal that an ELAVL2-directed post-transcriptional network is essential for the formation of quiescent primordial follicles.

Keywords: DDX6; ELAVL2; P-body-like granules; post-transcriptional gene regulation; primordial follicles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • ELAV-Like Protein 2 / genetics
  • ELAV-Like Protein 2 / metabolism*
  • Female
  • Gene Regulatory Networks*
  • Infertility, Female / genetics*
  • Mice
  • Oogenesis
  • Ovarian Follicle / cytology
  • Ovarian Follicle / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism

Substances

  • ELAV-Like Protein 2
  • Elavl2 protein, mouse
  • Proto-Oncogene Proteins
  • Ddx6 protein, mouse
  • DEAD-box RNA Helicases

Associated data

  • GEO/GSE112275
  • GEO/GSE113305