2. Academic Validation
  3. CNOT6/6L-mediated mRNA degradation in ovarian granulosa cells is a key mechanism of gonadotropin-triggered follicle development

CNOT6/6L-mediated mRNA degradation in ovarian granulosa cells is a key mechanism of gonadotropin-triggered follicle development

  • Cell Rep. 2021 Nov 16;37(7):110007. doi: 10.1016/j.celrep.2021.110007.
Xing-Xing Dai 1,  Zhi-Yan Jiang 1,  Yun-Wen Wu 1,  Qian-Qian Sha 2,  Yang Liu 3,  Jia-Yi Ding 3,  Wen-Dong Xi 4,  Jing Li 4,  Heng-Yu Fan 5
Affiliations

Affiliations

  • 1 Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
  • 2 Fertility Preservation Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou 510317, China.
  • 3 Department of Assisted Reproduction, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong 226000, China.
  • 4 State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211100, China.
  • 5 Life Sciences Institute, Zhejiang University, Hangzhou 310058, China. Electronic address: hyfan@zju.edu.cn.
PMID: 34788619 DOI: 10.1016/j.celrep.2021.110007
Abstract

CCR4-NOT deadenylase is a major regulator of mRNA turnover. It contains two heterogeneous catalytic subunits CNOT7/8 and CNOT6/6L in vertebrates. The physiological function of each catalytic subunit is unclear due to the gene redundancy. In this study, Cnot6/6l double knockout mice are generated. Cnot6l-/- female mice are infertile, with poor ovarian responses to gonadotropins. Follicle-stimulating hormone (FSH) stimulates the transcription and translation of Cnot6 and Cnot6l in ovarian granulosa cells. CNOT6/6L function as key effectors of FSH in granulosa cells and trigger the clearance of specific transcripts in granulosa cells during preantral to antral follicle transition. These results demonstrate that FSH modulates granulosa cell function by stimulating selective translational activation and degradation of existing mRNAs, in addition to inducing de novo gene transcription. Meanwhile, this study provides in vivo evidence that CNOT6/6L-mediated mRNA deadenylation is dispensable in most somatic cell types, but is essential for female reproductive endocrine regulation.

Keywords

PI3K signaling pathway; endocrine; female reproduction; follicle development; follicle-stimulating hormone; mRNA stability; mRNA translation; ovary; ovulation.

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