Ipa1 Is an RNA Polymerase II Elongation Factor that Facilitates Termination by Maintaining Levels of the Poly(A) Site Endonuclease Ysh1
Ipa1 Is an RNA Polymerase II Elongation Factor that Facilitates Termination by Maintaining Levels of the Poly(A) Site Endonuclease Ysh1
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DOI：
10.1016/j.celrep.2019.01.051
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发表时间：
2019-02-12
期刊：
影响因子：
8.8
通讯作者：
Moore, Claire L.
中科院分区：
文献类型：
--
作者：
Pearson, Erika L.;Graber, Joel H.;Moore, Claire L.
最近发现酵母蛋白Ipa 1与前体mRNA切割和多聚腺苷酸化（C/P）机制的Ysh 1内切酶相互作用，并且Ipa 1突变损害3'末端加工。我们报告说，Ipa 1全球促进适当的转录终止和聚（A）位点的选择，但与变量的影响，基因取决于聚腺苷酸化信号的具体配置。我们的研究结果表明，Ipa 1在终止中的作用是通过与Ysh 1的相互作用介导的，因为Ipa 1突变导致Ysh 1的减少和C/P复合物对转录基因的不良招募。Ipa 1与转录活性染色质的关联类似于延伸因子，并且突变体在体内显示有缺陷的Pol II延伸动力学。Ysh 1在Ipa 1突变体中的过表达挽救了终止缺陷，但不是突变体对6-azauracil的敏感性，这是有缺陷的延伸的指标。我们的研究结果支持了一个模型，其中Ipa 1/Ysh 1复合物有助于协调转录延伸和3'端加工。
The yeast protein Ipa1 was recently discovered to interact with the Ysh1 endonuclease of the pre-mRNA cleavage and polyadenylation (C/P) machinery, and Ipa1 mutation impairs 3' end processing. We report that Ipa1 globally promotes proper transcription termination and poly(A) site selection, but with variable effects on genes depending upon the specific configurations of polyadenylation signals. Our findings suggest that the role of Ipa1 in termination is mediated through interaction with Ysh1, since Ipa1 mutation leads to decrease in Ysh1 and poor recruitment of the C/P complex to a transcribed gene. The Ipa1 association with transcriptionally active chromatin resembles that of elongation factors, and the mutant shows defective Pol II elongation kinetics in vivo. Ysh1 overexpression in the Ipa1 mutant rescues the termination defect, but not the mutant's sensitivity to 6-azauracil, an indicator of defective elongation. Our findings support a model in which an Ipa1/Ysh1 complex helps coordinate transcription elongation and 3' end processing.