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Phase separation of Ddx3xb helicase regulates maternal-to-zygotic transition in zebrafish

Boyang Shi1,2,8,† , Jian Heng3,4,† , Jia-Yi Zhou1,2,5,† , Ying Yang1,2,4,5,† , Wan-Ying Zhang1,2,5 , Magdalena J. Koziol6 , Yong-Liang Zhao1,2,5 , Pilong Li7 , Feng Liu3,4,5,* , Yun-Gui Yang1,2,4,5,*

1CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
2China National Center for Bioinformation, Beijing, China
3State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
4Institute of Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China
5University of Chinese Academy of Sciences, Beijing, China
6Chinese Institute for Brain Research, Beijing, China
7Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China
8Present address: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
These authors contributed equally: Boyang Shi, Jian Heng, Jia-Yi Zhou, Ying Yang
* Correspondence: Feng Liu(liuf@ioz.ac.cn)Yun-Gui Yang(ygyang@big.ac.cn)

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.

https://doi.org/10.1038/s41422-022-00655-5

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