title: The E3 ubiquitin ligase RNF114 and TAB1 degradation are required for maternal-to-zygotic transition.
abstract: The functional role of the ubiquitin-proteasome pathway during maternal-to-zygotic transition (MZT) remains to be elucidated. Here we show that the E3 ubiquitin ligase, Rnf114, is highly expressed in mouse oocytes and that knockdown of Rnf114 inhibits development beyond the two-cell stage. To study the underlying mechanism, we identify its candidate substrates using a 9,000-protein microarray and validate them using an in vitro ubiquitination system. We show that five substrates could be degraded by RNF114-mediated ubiquitination, including TAB1. Furthermore, the degradation of TAB1 in mouse early embryos is required for MZT, most likely because it activates the NF-κB pathway. Taken together, our study uncovers that RNF114-mediated ubiquitination and degradation of TAB1 activate the NF-κB pathway during MZT, and thus directly link maternal clearance to early embryo development.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China.|Department of Reproduction, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China.|Department of Reproduction, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, the Chinese Academy of Science, Beijing, China.
authors.forename: Weixiao
authors.initials: W
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, the Chinese Academy of Science, Beijing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, the Chinese Academy of Science, Beijing, China.
authors.forename: Liying
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, the Chinese Academy of Science, Beijing, China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, the Chinese Academy of Science, Beijing, China.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Shang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China.
authors.forename: Mingrui
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, the Chinese Academy of Science, Beijing, China.
authors.forename: Yuanting
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Animal Core Facility, Nanjing Medical University, Nanjing, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Animal Core Facility, Nanjing Medical University, Nanjing, China.
authors.forename: Jianli
authors.initials: J
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China huoran@njmu.edu.cn leways@ioz.ac.cn.
authors.forename: Ran
authors.identifier: 0000-0001-5166-127X
authors.initials: R
authors.lastname: Huo
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, the Chinese Academy of Science, Beijing, China huoran@njmu.edu.cn leways@ioz.ac.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016000:Cluster Analysis; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D000072741:Maternal Inheritance; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D025821:Polyubiquitin / Q000378:metabolism; D059748:Proteolysis; D015398:Signal Transduction; D013379:Substrate Specificity; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D015053:Zygote / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016328:NF-kappa B; C531463:Tab1 protein, mouse; D025821:Polyubiquitin; D044767:Ubiquitin-Protein Ligases
keywords: NF‐κB pathway; RNF114; TAB1; maternal‐to‐zygotic transition; two‐cell‐stage arrest