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.

脊椎动物胚胎发生涉及一个保守且基本的过程，称为母体向合子转变（MZT），它标志着从母体因素主导状态到合子因素驱动状态的转变。然而，MZT 背后的确切机制仍然很大程度上未知。在这里，我们报道斑马鱼中的RNA解旋酶Ddx3xb通过其N末端固有无序区域（IDR）进行液-液相分离（LLPS），并且ATP含量的增加促进MZT过程中Ddx3xb的缩合。失去 LLPS 能力的 Ddx3xb 突变体无法挽救 Ddx3xb 缺陷胚胎的发育缺陷。有趣的是，FUS 或 hnRNPA1 的 IDR 可以在功能上取代 Ddx3xb 中的 N 端 IDR。Ddx3xb 的相分离促进母体 mRNA 5' UTR 结构的解旋，从而增强其翻译。我们的研究揭示了一种前所未有的机制，即 Ddx3xb 相分离通过促进母体 mRNA 翻译来调节 MZT。