Biosystems Science Course, Graduate School of Life Science, Hokkaido University, Sapporo 060-0810, Japan.
Development and Stem Cells Program and Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Victoria 3800, Australia.
J Cell Sci. 2020 Dec 11;133(23):jcs249128. doi: 10.1242/jcs.249128.
Temporal and spatial control of mRNA translation has emerged as a major mechanism for promoting diverse biological processes. However, the molecular nature of temporal and spatial control of translation remains unclear. In oocytes, many mRNAs are deposited as a translationally repressed form and are translated at appropriate times to promote the progression of meiosis and development. Here, we show that changes in subcellular structures and states of the RNA-binding protein pumilio 1 (Pum1) regulate the translation of target mRNAs and progression of oocyte maturation. Pum1 was shown to bind to (also known as ) and cyclin B1 mRNAs, assemble highly clustered aggregates, and surround and cyclin B1 RNA granules in mouse oocytes. These Pum1 aggregates were dissolved prior to the translational activation of target mRNAs, possibly through phosphorylation. Stabilization of Pum1 aggregates prevented the translational activation of target mRNAs and progression of oocyte maturation. Together, our results provide an aggregation-dissolution model for the temporal and spatial control of translation.
mRNA 翻译的时空调控已成为促进多种生物过程的主要机制。然而，翻译时空调控的分子性质尚不清楚。在卵母细胞中，许多 mRNA 以翻译抑制的形式存在，并在适当的时候被翻译，以促进减数分裂和发育的进行。在这里，我们表明 RNA 结合蛋白 pumilio 1（Pum1）的亚细胞结构和状态的变化调节靶 mRNA 的翻译和卵母细胞成熟的进程。研究表明 Pum1 与（也称为）和 cyclin B1 mRNAs 结合，组装成高度聚集的聚集体，并在小鼠卵母细胞中围绕和 cyclin B1 RNA 颗粒。这些 Pum1 聚集体在靶 mRNA 的翻译激活之前溶解，可能通过磷酸化。Pum1 聚集体的稳定阻止了靶 mRNA 的翻译激活和卵母细胞成熟的进程。总之，我们的研究结果为翻译的时空调控提供了一个聚集-溶解模型。
