Fbxo30 regulates chromosome segregation of oocyte meiosis

• Published in: Cellular and molecular life sciences : CMLS 2019-06, Vol.76 (11), p.2217-2229
• Main Authors: Jin, Yimei, Yang, Mo, Gao, Chang, Yue, Wei, Liang, Xiaoling, Xie, Bingteng, Zhu, Xiaohui, Fan, Shangrong, Li, Rong, Li, Mo
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Chromosome Segregation; Chromosomes; Chromosomes, Mammalian - metabolism; Chromosomes, Mammalian - ultrastructure; Cullin; Depletion; Embryogenesis; Embryonic growth stage; F-Box Proteins - antagonists & inhibitors; F-Box Proteins - genetics; F-Box Proteins - metabolism; Female; Fertilization; Gene Expression Regulation, Developmental; Genomes; Histone H3; Histones - genetics; Histones - metabolism; Immunoprecipitation; Life Sciences; Meiosis; Metaphase; Mice; Mice, Inbred ICR; mRNA Cleavage and Polyadenylation Factors - genetics; mRNA Cleavage and Polyadenylation Factors - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oocytes; Oocytes - metabolism; Oocytes - ultrastructure; Original; Original Article; Primary Cell Culture; Proteasomes; Proteins; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; RNA-Binding Proteins; Signal Transduction; Spectrometry; Stem-loop-binding protein; Substrates; Transcription; Tubulin - genetics; Tubulin - metabolism; Ubiquitin; Ubiquitin-protein ligase
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-019-03038-z

As the female gamete, meiotic oocytes provide not only half of the genome but also almost all stores for fertilization and early embryonic development. Because de novo mRNA transcription is absent in oocyte meiosis, protein-level regulations, especially the ubiquitin proteasome system, are more crucial. As the largest family of ubiquitin E3 ligases, Skp1–Cullin–F-box complexes recognize their substrates via F-box proteins with substrate-selected specificity. However, the variety of F-box proteins and their unknown substrates hinder our understanding of their functions. In this report, we find that Fbxo30, a new member of F-box proteins, is enriched in mouse oocytes, and its expression level declines substantially after the metaphase of the first meiosis (MI). Notably, depletion of Fbxo30 causes significant chromosome compaction accompanied by chromosome segregation failure and arrest at the MI stage, and this arrest is not caused by over-activation of spindle assembly checkpoint. Using immunoprecipitation and mass spectrometric analysis, we identify stem-loop-binding protein (SLBP) as a novel substrate of Fbxo30. SLBP overexpression caused by Fbxo30 depletion results in a remarkable overload of histone H3 on chromosomes that excessively condenses chromosomes and inhibits chromosome segregation. Our finding uncovers an unidentified pathway-controlling chromosome segregation and cell progress.