Identification of RNA-binding proteins involved in the formation and maintenance of egg precursors

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

Yuzuru Kato, Tokuko Iwamori, Yoichirou Ninomiya, Takashi Kohda, Jyunko Miyashita, Mikiko Sato, and Yumiko Saga

EMBO reports e48251, 2019 DOI:10.15252/embr.201948251

Long‐term reproduction of mammalian females is achieved by controlled sustainability and growth of the most primitive ovarian follicles called primordial follicles, which are composed of a single oocyte and a few of the supporting somatic cells, granulosa cells. Given the importance of primordial follicles as a finite reservoir of eggs in mammalian ovaries, understanding the molecular mechanisms underlying the formation and sustainability of primordial follicles is essential for reproductive biology and medicine.

Kato et al., demonstrated that RNA-binding proteins ELAVL2 and DDX6 drive the assembly of P-body-like cytoplasmic RNP granules in oocytes and the formation of primordial follicles collaborating with Kyushu university and Yamanashi University. The research group revealed that an RNA-binding protein ELAVL2 is indispensable for the formation of primordial follicles in mice. Subsequently, the group identified mRNAs that interact with ELAVL2, among which they found that mRNAs encoding components of cytoplasmic RNP granules such as P-bodies were enriched. Furthermore, deletion of Ddx6, one of the targets of ELAVL2 and a gene encoding crucial component of P-bodies, exhibited disassembly of P-body-like granules in oocytes and defective formation of primordial follicles. These findings revealed that the ELAVL2-directed post-transcriptional network is crucial for primordial follicle formation.

This study was supported by Grant-in-Aid for Scientific Research (C) to Y.K. (No.17K07422) and (A) to Y.S. (No.26251025) from JSPS and by Grant-in-Aid for Scientific Research on Innovative Area to Y.K. (No.26114512, 16H01259, 19H05246) and T.I. (No.26114506) from MEXT.


Figure: Primordial follicles arise from oocyte in cyst shortly after birth. In oocytes, large P-body-like cytoplsamic RNP granules are formed depending on the function of RNA-binding proteins ELAVL2 and DDX6. Deletion of Elavl2 or Ddx6 results in the defective assembly of the granules and the formation of primordial follicles in mice.

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