m 6 A reader protein YTHDF2 regulates spermatogenesis by timely clearance of phase-specific transcripts.

Autor: Qi M; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.; Center for Reproductive Medicine, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China., Sun H; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China., Guo Y; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China., Zhou Y; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China., Gu X; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China., Jin J; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China., Chen X; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China., Wang F; Reproductive Medicine Center, Gansu Provincial Maternity and Child-Care Hospital, Lanzhou, China., Ma H; Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China., Guo X; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China., Chen H; Department of Human Cell Biology and Genetics, School of Medicine, Southern University of Science and Technology, Shenzhen, China., Shen B; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.; Gusu School, Nanjing Medical University, Nanjing, China.; Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.; Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China.
Jazyk: angličtina
Zdroj: Cell proliferation [Cell Prolif] 2022 Jan; Vol. 55 (1), pp. e13164. Date of Electronic Publication: 2021 Nov 30.
DOI: 10.1111/cpr.13164
Abstrakt: Objectives: Accumulating evidences show that the regulatory network of m 6 A modification is essential for mammalian spermatogenesis. However, as an m 6 A reader, the roles of YTHDF2 remain enigmatic due to the lack of a proper model. Here, we employed the germ cell conditional knockout mouse model and explored the function of YTHDF2 in spermatogenesis.
Materials and Methods: Ythdf2 germ cell conditional knockout mice were obtained by crossing Ythdf2-floxed mice with Vasa-Cre and Stra8-Cre mice. Haematoxylin and eosin (HE) staining, immunofluorescent staining and Western blotting were used for phenotyping. CASA, IVF and ICSI were applied for sperm function analysis. RNA-seq, YTHDF2-RIP-seq and quantitative real-time PCR were used to explore transcriptome changes and molecular mechanism analysis.
Results: Our results showed that YTHDF2 was highly expressed in spermatogenic cells. The germ cell conditional knockout males were sterile, and their sperm displayed malformation, impaired motility, and lost fertilization ability. During differentiated spermatogonia transiting to pachytene spermatocyte, most m 6 A-modified YTHDF2 targets that were degraded in control germ cells persisted in pachytene spermatocytes of Ythdf2-vKO mice. These delayed mRNAs were mainly enriched in pathways related to the regulation of transcription, and disturbed the transcriptome of round spermatid and elongated spermatid subsequently.
Conclusion: Our data demonstrate that YTHDF2 facilitates the timely turnover of phase-specific transcripts to ensure the proper progression of spermatogenesis, which highlights a critical role of YTHDF2 in spermatogenesis.
(© 2021 The Authors. Cell Proliferation published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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