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Comment |
Maternal RNF114-mediated target substrate degradation regulates zygotic genome activation in mouse embryos. Zhou S et al. (2021) 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 2-cell embryos developmental arrest in mice. RNF114 was proven to play a crucial role in major ZGA using immunofluorescence and transcriptome analysis. To study the underlying mechanism, we performed protein profiling in mature oocytes and found a potential substrate for RNF114, Chromobox 5 (CBX5), whose ubiquitination and degradation was regulated by RNF114. The overexpression of CBX5 prevented embryonic development and impeded major ZGA. Furthermore, TAB1 was abnormally accumulated in mutant 2-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 MZT, the mis-regulation of which may impede the appropriate activation of major ZGA in mouse embryos.//////////////////The E3 ubiquitin ligase RNF114 and TAB1 degradation are required for maternal-to-zygotic transition. Yang Y et al. (2017) 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.//////////////////
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