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

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.

A Potential Role for the Gsdf–eEF1α Complex in Inhibiting Germ Cell Proliferation: A Protein-Interaction Analysis in Medaka (Oryzias latipes) From a Proteomics Perspective

“…S2 ), while the physical interaction ability between Gsdf and 42Sp50 was verified by Y2H (date not published), suggesting that the transfer of Gsdf binding from eEF1α to 42Sp50 may play an important role in the transition of gametogenesis from spermatogenesis to oogenesis. In addition, Ddx6 and Elavl2, the RNA-binding proteins indispensable for the formation of quiescent primordial follicles in mice ( 36 ), were elevated in gsdf -deficient ovaries ( Fig. 4 ).…”

Establishing and maintaining fertility: the importance of cell cycle arrest

“…Irx3 is specifically expressed in the intercellular bridges of germ cell nests, and when both Irx3 and Irx5 are deleted, defective granulosa cells fail to connect with the oocyte, causing aberrant follicle formation and apoptosis of the developing follicles (Fu et al 2018). Other factors are specific to the signals originating from the oocyte, including factors like ELAV-like protein 2 (ELAVL2) and DEAD-box helicase 6 (DDX6) (Kato et al 2019). Loss of ELAVL2 or DDX6 in isolation both lead to an infertility phenotype in mice, with no oocytes remaining in the ovary 2 wk after birth due to a defect in primordial follicle formation (Kato et al 2019).…”

“…Other factors are specific to the signals originating from the oocyte, including factors like ELAV-like protein 2 (ELAVL2) and DEAD-box helicase 6 (DDX6) (Kato et al 2019). Loss of ELAVL2 or DDX6 in isolation both lead to an infertility phenotype in mice, with no oocytes remaining in the ovary 2 wk after birth due to a defect in primordial follicle formation (Kato et al 2019). Together these studies show that the maintenance of granulosa-oocyte communication is essential for germ cell nest breakdown and follicle formation.…”

Regulation of primordial follicle formation, dormancy, and activation in mice

“…ELAV-like RNA binding protein 1 (ELAVL2) is an RNA-binding protein that directs the assembly of P-bodies by promoting the translation of DEAD (Asp-Glu-Ala-Asp) box polypeptide 6 (DDX6). Both ELAVL2 and DDX6 are indispensable for the formation of quiescent primordial follicles [ 26 ]. Notably, DDX6-deficient mice showed a dysregulation of PI3K-AKT signaling in primordial follicles.…”