Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France.
Equipe Labélisée Ligue Nationale Contre le Cancer, University of Montpellier, CNRS, Montpellier, France.
Nat Commun. 2021 Mar 1;12(1):1352. doi: 10.1038/s41467-021-21585-7.
Local translation allows for a spatial control of gene expression. Here, we use high-throughput smFISH to screen centrosomal protein-coding genes, and we describe 8 human mRNAs accumulating at centrosomes. These mRNAs localize at different stages during cell cycle with a remarkable choreography, indicating a finely regulated translational program at centrosomes. Interestingly, drug treatments and reporter analyses reveal a common translation-dependent localization mechanism requiring the nascent protein. Using ASPM and NUMA1 as models, single mRNA and polysome imaging reveals active movements of endogenous polysomes towards the centrosome at the onset of mitosis, when these mRNAs start localizing. ASPM polysomes associate with microtubules and localize by either motor-driven transport or microtubule pulling. Remarkably, the Drosophila orthologs of the human centrosomal mRNAs also localize to centrosomes and also require translation. These data identify a conserved family of centrosomal mRNAs that localize by active polysome transport mediated by nascent proteins.
本地化翻译可以实现基因表达的空间控制。在这里,我们使用高通量 smFISH 筛选中心体蛋白编码基因,并描述了 8 个人类 mRNA 在中心体中积累。这些 mRNA 在细胞周期的不同阶段定位于不同的位置,具有显著的协调作用,表明中心体存在精细调控的翻译程序。有趣的是,药物处理和报告分析揭示了一种常见的依赖翻译的定位机制,需要新生蛋白。使用 ASPM 和 NUMA1 作为模型,单 mRNA 和多核糖体成像显示,在有丝分裂开始时,当这些 mRNA 开始定位时,内源性多核糖体向中心体的主动运动。ASPM 多核糖体与微管结合,并通过驱动蛋白驱动的运输或微管牵引定位。值得注意的是,人类中心体 mRNA 的果蝇同源物也定位于中心体,并且也需要翻译。这些数据确定了一组保守的中心体 mRNA,它们通过由新生蛋白介导的活跃多核糖体运输定位。