ELAVL2‐directed RNA regulatory network drives the formation of quiescent primordial follicles. (28th October 2019)

• Record Type: Journal Article
• Authors: Kato, Yuzuru; Iwamori, Tokuko; Ninomiya, Youichirou; Kohda, Takashi; Miyashita, Jyunko; Sato, Mikiko; Saga, Yumiko
• Is Part Of: EMBO reports. Volume 20:Number 12(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-10-28
• Subjects: DDX6 -- ELAVL2 -- P‐body‐like granules -- post‐transcriptional gene regulation -- primordial follicles; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201948251
• Languages: English
• ISSNs: 1469-221X

Abstract

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. Synopsis: The RNA‐binding proteins ELAVL2 and DDX6 drive the assembly of large P body‐like cytoplasmic RNP granules in oocytes and the formation of quiescent primordial follicles. ELAVL2 is required for the formation of primordial follicles in mice. Large P body‐like granules are assembled in oocytes prior to the formation of primordial follicles in an ELAVL2‐dependent manner. ELAVL2‐dependent DDX6 translation is crucial for the assembly of P body‐like granules. DDX6 is required for maintaining the quiescent state of primordial follicles. Abstract : The RNA‐binding proteins ELAVL2 and DDX6 drive the assembly of large P body‐like cytoplasmic RNP granules in oocytes and the formation of quiescent primordial follicles.