Department of Cell Biology, Emory University School of Medicine, Atlanta, GA.
J Cell Biol. 2020 Dec 7;219(12). doi: 10.1083/jcb.202004101.
Centrosomes are microtubule-organizing centers required for error-free mitosis and embryonic development. The microtubule-nucleating activity of centrosomes is conferred by the pericentriolar material (PCM), a composite of numerous proteins subject to cell cycle-dependent oscillations in levels and organization. In diverse cell types, mRNAs localize to centrosomes and may contribute to changes in PCM abundance. Here, we investigate the regulation of mRNA localization to centrosomes in the rapidly cycling Drosophila melanogaster embryo. We find that RNA localization to centrosomes is regulated during the cell cycle and developmentally. We identify a novel role for the fragile-X mental retardation protein in the posttranscriptional regulation of a model centrosomal mRNA, centrocortin (cen). Further, mistargeting cen mRNA is sufficient to alter cognate protein localization to centrosomes and impair spindle morphogenesis and genome stability.
中心体是有丝分裂和胚胎发育过程中维持染色体正确分离所必需的微管组织中心。中心体的微管成核活性由中心粒周围物质(PCM)赋予,PCM 是许多蛋白质的复合物,其水平和组织在细胞周期中呈波动变化。在不同的细胞类型中,mRNA 定位于中心体,可能有助于 PCM 丰度的变化。在这里,我们研究了在快速分裂的果蝇胚胎中 mRNA 定位于中心体的调控机制。我们发现,mRNA 定位于中心体是在细胞周期和发育过程中受到调控的。我们发现脆性 X 智力低下蛋白(fragile-X mental retardation protein)在一个模型的中心体 mRNA(centrocortin,cen)的转录后调控中具有新的作用。此外,cen mRNA 的靶向错误足以改变同源蛋白在中心体的定位,并损害纺锤体形态发生和基因组稳定性。