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EDC-3 和 EDC-4 调控胚胎 mRNA 清除和生物分子凝聚物的特化。

EDC-3 and EDC-4 regulate embryonic mRNA clearance and biomolecular condensate specialization.

机构信息

Department of Biochemistry, McGill University, Montréal QC H3G 1Y6, Canada; Rosalind and Morris Goodman Cancer Institute, Montréal QC H3G 1Y6, Canada.

Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

出版信息

Cell Rep. 2024 Oct 22;43(10):114781. doi: 10.1016/j.celrep.2024.114781. Epub 2024 Sep 25.

Abstract

Animal development is dictated by the selective and timely decay of mRNAs in developmental transitions, but the impact of mRNA decapping scaffold proteins in development is unclear. This study unveils the roles and interactions of the DCAP-2 decapping scaffolds EDC-3 and EDC-4 in the embryonic development of C. elegans. EDC-3 facilitates the timely removal of specific embryonic mRNAs, including cgh-1, car-1, and ifet-1 by reducing their expression and preventing excessive accumulation of DCAP-2 condensates in somatic cells. We further uncover a role for EDC-3 in defining the boundaries between P bodies, germ granules, and stress granules. Finally, we show that EDC-4 counteracts EDC-3 and engenders the assembly of DCAP-2 with the GID (CTLH) complex, a ubiquitin ligase involved in maternal-to-zygotic transition (MZT). Our findings support a model where multiple RNA decay mechanisms temporally clear maternal and zygotic mRNAs throughout embryonic development.

摘要

动物的发育是由 mRNA 在发育转变中的选择性和适时降解所决定的,但 mRNA 脱帽支架蛋白在发育中的作用尚不清楚。本研究揭示了 DCAP-2 脱帽支架 EDC-3 和 EDC-4 在 C. elegans 胚胎发育中的作用和相互作用。EDC-3 通过降低其表达并防止 DCAP-2 凝聚物在体细胞中过度积累,促进特定胚胎 mRNA(包括 cgh-1、car-1 和 ifet-1)的适时去除。我们进一步发现 EDC-3 在界定 P 体、生殖颗粒和应激颗粒之间的边界方面发挥作用。最后,我们表明 EDC-4 拮抗 EDC-3,并促使 DCAP-2 与 GID(CTLH)复合物组装,该复合物是一种参与母源到合子过渡(MZT)的泛素连接酶。我们的研究结果支持了这样一种模型,即多个 RNA 降解机制在胚胎发育过程中适时清除母源和合子 mRNA。

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