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Core Exosome-independent Roles for Rrp6 in Cell Cycle Progression

机译:Rrp6在细胞周期进程中的核心外泌体无关的作用。

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Exosome complexes are 3′ to 5′ exoribonucleases composed of subunits that are critical for numerous distinct RNA metabolic (ribonucleometabolic) pathways. Several studies have implicated the exosome subunits Rrp6 and Dis3 in chromosome segregation and cell division but the functional relevance of these findings remains unclear. Here, we report that, in Drosophila melanogaster S2 tissue culture cells, dRrp6 is required for cell proliferation and error-free mitosis, but the core exosome subunit Rrp40 is not. Micorarray analysis of dRrp6-depleted cell reveals increased levels of cell cycle– and mitosis-related transcripts. Depletion of dRrp6 elicits a decrease in the frequency of mitotic cells and in the mitotic marker phospho-histone H3 (pH3), with a concomitant increase in defects in chromosome congression, separation, and segregation. Endogenous dRrp6 dynamically redistributes during mitosis, accumulating predominantly but not exclusively on the condensed chromosomes. In contrast, core subunits localize predominantly to MTs throughout cell division. Finally, dRrp6-depleted cells treated with microtubule poisons exhibit normal kinetochore recruitment of the spindle assembly checkpoint protein BubR1 without restoring pH3 levels, suggesting that these cells undergo premature chromosome condensation. Collectively, these data support the idea that dRrp6 has a core exosome-independent role in cell cycle and mitotic progression.
机译:外泌体复合物是3'至5'外核糖核酸酶,由对许多不同的RNA代谢(核糖代谢)途径至关重要的亚基组成。几项研究已将外泌体亚基Rrp6和Dis3牵涉到染色体分离和细胞分裂,但这些发现的功能相关性尚不清楚。在这里,我们报告说,在果蝇S2组织培养细胞中,dRrp6是细胞增殖和无错误有丝分裂所必需的,但核心外泌体亚基Rrp40不是必需的。对缺失dRrp6的细胞进行的微阵列分析表明,细胞周期和有丝分裂相关的转录本水平有所提高。 dRrp6的消耗会导致有丝分裂细胞和有丝分裂标记物磷酸组蛋白H3(pH3)的频率降低,并伴随着染色体聚集,分离和分离缺陷的增加。内源性dRrp6在有丝分裂过程中动态地重新分布,主要但并非唯一地聚集在浓缩染色体上。相反,在整个细胞分裂过程中,核心亚基主要定位于MT。最后,用微管中毒处理的dRrp6耗尽的细胞表现出纺锤体装配检查点蛋白BubR1正常的动线粒募集,而没有恢复pH3的水平,表明这些细胞经历了早熟的染色体浓缩。总体而言,这些数据支持dRrp6在细胞周期和有丝分裂进程中具有核心外泌体非依赖性作用的观点。

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