Volume 32, No 8, Aug 2022

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 32 Issue 8, August 2022: 715-728

ORIGINAL ARTICLES

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

Boyang Shi^1,2,8,† , Jian Heng^3,4,† , Jia-Yi Zhou^1,2,5,† , Ying Yang^1,2,4,5,† , Wan-Ying Zhang^1,2,5 , Magdalena J. Koziol⁶ , Yong-Liang Zhao^1,2,5 , Pilong Li⁷ , Feng Liu^3,4,5,* , Yun-Gui Yang^1,2,4,5,*

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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