Exonuclease domain mutants of yeast DIS3 display genome instability
Exonuclease domain mutants of yeast DIS3 display genome instability
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DOI：
10.1080/19491034.2019.1578600
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发表时间：
2019-01-01
期刊：
影响因子：
3.7
通讯作者：
Stirling, Peter C.
中科院分区：
文献类型：
--
作者：
Milbury, Karissa L.;Paul, Biplab;Stirling, Peter C.
外泌体的功能是通过RNA生物合成、监视和衰变来调节细胞转录组。Dis 3是RNA外泌体的催化亚基，具有可分离的核酸内切酶和核酸外切酶活性，其突变与多发性骨髓瘤有关。在这里，我们报告了一个癌症相关的DIS 3等位基因，dis 3（E729 K），DIS 3在酵母有丝分裂保真度的功能提供了证据。该dis 3（E729 K）等位基因不诱导7S -> 5.8S rRNA加工中的缺陷，尽管它引起P体功能的需要。虽然它不显着影响细胞周期的进程单独，等位基因降低了细胞周期停滞的效率，在动粒装配缺陷的菌株。最后，酵母Dis 3的核酸外切酶结构域中的点突变引起基因组不稳定性表型;然而，这些DIS 3突变不会增加DNA损伤或RNA加工缺陷，从而导致多聚腺苷酸化RNA在细胞核中的积累。这些数据表明，特定的DIS 3活动支持酵母中的有丝分裂保真度。
The exosome functions to regulate the cellular transcriptome through RNA biogenesis, surveillance, and decay. Mutations in Dis3, a catalytic subunit of the RNA exosome with separable endonuclease and exonuclease activities, are linked to multiple myeloma. Here we report that a cancer-associated DIS3 allele, dis3(E729K), provides evidence for DIS3 functioning in mitotic fidelity in yeast. This dis3(E729K) allele does not induce defects in 7S -> 5.8S rRNA processing, although it elicits a requirement for P-body function. While it does not significantly influence cell cycle progression alone, the allele reduces the efficiency of cell cycle arrest in strains with defects in kinetochore assembly. Finally, point mutations in the exonuclease domains of yeast Dis3 elicit genome instability phenotypes; however, these DIS3 mutations do not increase DNA damage or RNA processing defects that lead to the accumulation of polyadenylated RNA in the nucleus. These data suggest that specific DIS3 activities support mitotic fidelity in yeast.