Vertebrate embryogenesis involves a conserved and fundamental process, called the maternal-to-zygotic transition (MZT), which marks the switch from a maternal factors-dominated state to a zygotic factors-driven state. Yet the precise mechanism underlying MZT remains largely unknown. Here we report that the RNA helicase Ddx3xb in zebrafish undergoes liquid–liquid phase separation (LLPS) via its N-terminal intrinsically disordered region (IDR), and an increase in ATP content promotes the condensation of Ddx3xb during MZT. Mutant form of Ddx3xb losing LLPS ability fails to rescue the developmental defect of Ddx3xb-deficient embryos. Interestingly, the IDR of either FUS or hnRNPA1 can functionally replace the N-terminal IDR in Ddx3xb. Phase separation of Ddx3xb facilitates the unwinding of 5’ UTR structures of maternal mRNAs to enhance their translation. Our study reveals an unprecedent mechanism whereby the Ddx3xb phase separation regulates MZT by promoting maternal mRNA translation.
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The RNA-seq, RIP, and ribosome profiling data supporting the conclusions of this article have been deposited in the Gene Expression Omnibus database (GEO: GSE169169), and also the Genome Sequence Archive (GSA: CRA003999 linked to the BioProject with accession Number PRJCA004602).
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This work was supported by grants from the National Natural Science Foundation of China (32030058, 32121001, 31625016, 32030032), the Strategic Priority Research Program of the Chinese Academy of Sciences, China (XDA16010207, XDA16010501, XDPB2004), the National Key R&D Program of China (2018YFA0800200, 2019YFA0110901), the Youth Innovation Promotion Association of Chinese Academy of Sciences (2018133), Shanghai Municipal Science and Technology Major Project (2017SHZDZX01), and Research Unit of Medical Neurobiology, Chinese Academy of Medical Sciences (2019RU003).
The authors declare no competing interests.
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Shi, B., Heng, J., Zhou, JY. et al. Phase separation of Ddx3xb helicase regulates maternal-to-zygotic transition in zebrafish. Cell Res 32, 715–728 (2022). https://doi.org/10.1038/s41422-022-00655-5
Cell Research (2022)