The crucial role of HFM1 in regulating FUS ubiquitination and localization for oocyte meiosis prophase I progression in mice

• Published in: Biological research 2024-05, Vol.57 (1), p.36-17, Article 36
• Main Authors: Zhong, Chenyi, Wang, Huiyuan, Yuan, Xiong, He, Yuheng, Cong, Jing, Yang, Rui, Ma, Wenjie, Gao, Li, Gao, Chao, Cui, Yugui, Wu, Jie, Tan, Rongrong, Pu, Danhua
• Format: Article
• Language: English
• Subjects: Adenoviruses; Animals; Antibodies; Apoptosis; Apoptosis - physiology; BRCA1 protein; Chromosomes; DNA Breaks, Double-Stranded; DNA damage; DNA helicase; DNA repair; DNA Repair - physiology; Double-strand break repair; Etiology; Female; Females; FUS; FUS protein; Genes; HFM1; Humidity; Laboratory animals; Localization; Meiosis; Meiosis - physiology; Meiosis prophase I; Meiotic Prophase I - physiology; Mice; Mice, Knockout; Molecular modelling; Oocyte; Oocytes; Oocytes - metabolism; Ovaries; Pachytene; Polymerase chain reaction; Premature ovarian failure/insufficiency; Prophase; Proteins; RNA-Binding Protein FUS - genetics; RNA-Binding Protein FUS - metabolism; Spermatogenesis; Ubiquitin; Ubiquitination
• ISSN: 0717-6287; 0716-9760; 0717-6287
• DOI: 10.1186/s40659-024-00518-w

Helicase for meiosis 1 (HFM1), a putative DNA helicase expressed in germ-line cells, has been reported to be closely associated with premature ovarian insufficiency (POI). However, the underlying molecular mechanism has not been clearly elucidated. The aim of this study was to investigate the function of HFM1 in the first meiotic prophase of mouse oocytes. The results suggested that the deficiency of HFM1 resulting in increased apoptosis and depletion of oocytes in mice, while the oocytes were arrested in the pachytene stage of the first meiotic prophase. In addition, impaired DNA double-strand break repair and disrupted synapsis were observed in the absence of HFM1. Further investigation revealed that knockout of HFM1 promoted ubiquitination and degradation of FUS protein mediated by FBXW11. Additionally, the depletion of HFM1 altered the intranuclear localization of FUS and regulated meiotic- and oocyte development-related genes in oocytes by modulating the expression of BRCA1. These findings elaborated that the critical role of HFM1 in orchestrating the regulation of DNA double-strand break repair and synapsis to ensure meiosis procession and primordial follicle formation. This study provided insights into the pathogenesis of POI and highlighted the importance of HFM1 in maintaining proper meiotic function in mouse oocytes.