期刊
DEVELOPMENT
卷 148, 期 13, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.199426
关键词
Maternal RNF114; Zygotic genomic activation; Preimplantation embryo development; Ubiquitin degradation; CBX5; TAB1
资金
- National Key Research and Development Program of China [2018YFC1004002]
- National Natural Science Foundation of China [31671566, 32070838]
- Postgraduate Education Reform Project of Jiangsu Province [KYCX19_1144]
- Open Fund of State Key Laboratory of Reproductive Medicine of Nanjing Medical University [SKLRM-201806]
The study reveals that maternal RNF114 plays a crucial role in degrading important substrates during the maternal-to-zygotic transition, regulating the activation of major ZGA in mouse embryos. Misregulation of this process may impede appropriate ZGA activation.
Zygotic genomic activation (ZGA) is a landmark event in the maternal-to-zygotic transition (MZT), and the regulation of ZGA by maternal factors remains to be elucidated. In this study, the depletion of maternal ring finger protein 114 (RNF114), a ubiquitin E3 ligase, led to developmental arrest of two-cell mouse embryos. Using immunofluorescence and transcriptome analysis, RNF114 was proven to play a crucial role in major ZGA. To study the underlying mechanism, we performed protein profiling in mature oocytes and found a potential substrate for RNF114, chromobox 5 (CBX5), ubiquitylation and degradation of which was regulated by RNF114. The overexpression of CBX5 prevented embryonic development and impeded major ZGA. Furthermore, TAB1 was abnormally accumulated in mutant two-cell embryos, which was consistent with the result of in vitro knockdown of Rnf114. Knockdown of Cbx5 or Tab1 in maternal RNF114-depleted embryos partially rescued developmental arrest and the defect of major ZGA. In summary, our study reveals that maternal RNF114 plays a precise role in degrading some important substrates during the MZT, the misregulation of which may impede the appropriate activation of major ZGA in mouse embryos.
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