TY - JOUR
T1 - ELAVL2-directed RNA regulatory network drives the formation of quiescent primordial follicles
AU - Kato, Yuzuru
AU - Iwamori, Tokuko
AU - Ninomiya, Youichirou
AU - Kohda, Takashi
AU - Miyashita, Jyunko
AU - Sato, Mikiko
AU - Saga, Yumiko
N1 - Funding Information:
We thank D. H. Castrillon for kindly providing Mvh‐Cre mice. We also thank A. Suzuki for providing the DAZL antibody and A. Nakamura for critical reading of the manuscript. This work was supported by a Grant‐in‐Aid for Scientific Research to Y.K. (No. 17K07422) and Y.S. (No. 26251025) from JSPS, and by a Grant‐in‐Aid for Scientific Research on Innovative Areas from MEXT to Y.K. (No. 26114512, 16H01259, and 19H05247) and T.I. (No. 26114506).
Publisher Copyright:
© 2019 The Authors
PY - 2019/12/5
Y1 - 2019/12/5
N2 - 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.
AB - 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.
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U2 - 10.15252/embr.201948251
DO - 10.15252/embr.201948251
M3 - Article
C2 - 31657143
AN - SCOPUS:85074571539
SN - 1469-221X
VL - 20
JO - EMBO Reports
JF - EMBO Reports
IS - 12
M1 - e48251
ER -