Mutation of the essential yeast protein Ipa1 has previously been demonstrated to cause defects in pre-mRNA 3' end processing and growth, but the mechanism underlying these defects was not clear. In this study, we show that the ipa1-1 mutation causes a striking depletion of Ysh1, the evolutionarily conserved endonuclease subunit of the 19-subunit mRNA Cleavage/Polyadenylation (C/P) complex, but does not decrease other C/P subunits. YSH1 overexpression rescues both the growth and 3' end processing defects of the ipa1-1 mutant. YSH1 mRNA level is unchanged in ipa1-1 cells, and proteasome inactivation prevents Ysh1 loss and causes accumulation of ubiquitinated Ysh1. Ysh1 ubiquitination is mediated by the Ubc4 ubiquitin-conjugating enzyme and Mpe1, which in addition to its function in C/P, is also a RING ubiquitin ligase. In summary, Ipa1 affects mRNA processing by controlling the availability of the C/P endonuclease and may represent a regulatory mechanism that could be rapidly deployed to facilitate reprogramming of cellular responses.

中文翻译：

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泛素介导的降解对mRNA切割/聚腺苷酸化复合物的Ysh1核酸内切酶的调节。

先前已证明必需酵母蛋白Ipa1的突变会导致前mRNA 3'末端加工和生长中的缺陷，但尚不清楚这些缺陷的潜在机制。在这项研究中，我们表明，ipa1-1突变会引起Ysh1的惊人消耗，Ysh1是19个亚基mRNA裂解/多腺苷酸化（C / P）复合物的进化保守核酸内切酶亚基，但不会减少其他C / P亚基。YSH1过表达可以挽救ipa1-1突变体的生长和3'末端加工缺陷。在ipa1-1细胞中，YSH1 mRNA水平没有变化，蛋白酶体的失活可防止Ysh1丢失并引起泛素化Ysh1的积累。Ysh1泛素化由Ubc4泛素结合酶和Mpe1介导，Mpe1除了在C / P中的功能外，还是RING泛素连接酶。综上所述，