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PCM支架可使RNA定位于中心体。

The PCM scaffold enables RNA localization to centrosomes.

作者信息

Fang Junnan, Tian Weiyi, Quintanilla Melissa A, Beach Jordan R, Lerit Dorothy A

机构信息

Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322.

Equal contributions.

出版信息

bioRxiv. 2024 Jan 14:2024.01.13.575509. doi: 10.1101/2024.01.13.575509.

Abstract

As microtubule-organizing centers, centrosomes direct assembly of the bipolar mitotic spindle required for chromosome segregation and genome stability. Centrosome activity requires the dynamic assembly of pericentriolar material (PCM), the composition and organization of which changes throughout the cell cycle. Recent studies highlight the conserved localization of several mRNAs encoded from centrosome-associated genes enriched at centrosomes, including () mRNA. However, relatively little is known about how RNAs localize to centrosomes and influence centrosome function. Here, we examine mechanisms underlying the subcellular localization of mRNA. We find that mRNA localization is puromycin-sensitive, and the coding sequence is both necessary and sufficient for RNA localization, consistent with a co-translational transport mechanism. We identify regions within the coding sequence that regulate mRNA localization. Finally, we show that protein-protein interactions critical for elaboration of the PCM scaffold permit RNA localization to centrosomes. Taken together, these findings inform the mechanistic basis of mRNA localization and lend insight into the oscillatory enrichment of RNA at centrosomes.

摘要

作为微管组织中心,中心体指导染色体分离和基因组稳定性所需的双极有丝分裂纺锤体的组装。中心体活性需要中心粒周围物质(PCM)的动态组装,其组成和组织在整个细胞周期中都会发生变化。最近的研究强调了几种由富集在中心体的中心体相关基因编码的mRNA的保守定位,包括()mRNA。然而,关于RNA如何定位到中心体并影响中心体功能,人们所知相对较少。在这里,我们研究了mRNA亚细胞定位的潜在机制。我们发现mRNA定位对嘌呤霉素敏感,并且编码序列对于RNA定位既必要又充分,这与共翻译转运机制一致。我们确定了编码序列中调节mRNA定位的区域。最后,我们表明对PCM支架形成至关重要的蛋白质-蛋白质相互作用允许RNA定位到中心体。综上所述,这些发现揭示了mRNA定位的机制基础,并为RNA在中心体的振荡富集提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/704e/10926663/9cffaa9a5160/nihpp-2024.01.13.575509v1-f0001.jpg

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