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蓬乱的RNA结合蛋白揭示了中心粒过度复制中的局部翻译程序。

The Unkempt RNA binding protein reveals a local translation program in centriole overduplication.

作者信息

Martinez Abraham, Stemm-Wolf Alexander J, Sheridan Ryan M, Taliaferro Matthew J, Pearson Chad G

机构信息

Department of Cell and Developmental Biology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045.

RNA Bioscience Initiative (RBI), University of Colorado, Anschutz Medical Campus, Aurora CO 80045.

出版信息

bioRxiv. 2024 Jul 30:2024.07.29.605660. doi: 10.1101/2024.07.29.605660.

Abstract

Excess centrosomes cause defects in mitosis, cell-signaling, and cell migration, and therefore their assembly is tightly regulated. Plk4 controls centriole duplication at the heart of centrosome assembly, and elevation of Plk4 promotes centrosome amplification (CA), a founding event of tumorigenesis. Here, we investigate the transcriptional consequences of elevated Plk4 and find Unkempt, a gene encoding an RNA binding protein with roles in translational regulation, to be one of only two upregulated mRNAs. Unk protein localizes to centrosomes and Cep131-positive centriolar satellites and is required for Plk4-induced centriole overduplication in an RNA-binding dependent manner. Translation is enriched at centrosomes and centriolar satellites with Unk and Cep131 promoting this localized translation. A transient centrosomal downregulation of translation occurs early in Plk4-induced CA. CNOT9, an Unk interactor and component of the translational inhibitory CCR4-NOT complex, localizes to centrosomes at this time. In summary, centriolar satellites and Unk promote local translation as part of a translational program that ensures centriole duplication.

摘要

过多的中心体可导致有丝分裂、细胞信号传导和细胞迁移出现缺陷,因此其组装受到严格调控。Plk4在中心体组装的核心环节控制中心粒复制,Plk4水平升高会促进中心体扩增(CA),这是肿瘤发生的起始事件。在此,我们研究了Plk4水平升高后的转录后果,发现Unkempt是仅有的两个上调mRNA之一,该基因编码一种在翻译调控中发挥作用的RNA结合蛋白。Unk蛋白定位于中心体和Cep131阳性的中心粒卫星体,并且以RNA结合依赖的方式参与Plk4诱导的中心粒过度复制。在中心体和中心粒卫星体处,翻译过程因Unk和Cep131而富集,它们促进了这种局部翻译。在Plk4诱导的中心体扩增早期,会出现短暂的中心体翻译下调。此时,Unk相互作用蛋白及翻译抑制性CCR4-NOT复合体的组成部分CNOT9定位于中心体。总之,作为确保中心粒复制的翻译程序的一部分,中心粒卫星体和Unk促进局部翻译。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bf7/11312568/4e33a87ed551/nihpp-2024.07.29.605660v1-f0001.jpg

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