Regulation of the association of the PAF53/PAF49 heterodimer with RNA polymerase I.
Regulation of the association of the PAF53/PAF49 heterodimer with RNA polymerase I.
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PAF53/PAF49 异二聚体与 RNA 聚合酶 I 关联的调节。
DOI：
10.1016/j.gene.2014.09.022
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发表时间：
2015
期刊：
影响因子：
3.5
通讯作者：
Rothblum,LawrenceI
中科院分区：
文献类型：
--
作者：
Penrod,Yvonne;Rothblum,Katrina;Cavanaugh,Alice;Rothblum,LawrenceI
哺乳动物PAF 49和PAF 53形成异源二聚体并且对于转录是必需的。然而，它们在转录中的作用尚未明确定义。虽然酵母同源物是“非必需”蛋白质，但缺乏PAF 53同源物的酵母细胞在30 °C下以野生型速率的50-66%生长，但在25 °C下不能生长（Liljelund等人，1992; Beckouet等人，2008年）。越来越多的证据表明这些蛋白在转录起始和延伸过程中起重要作用，我们发现，虽然有些细胞调节PAF 53和PAF 49的蛋白水平，但其他细胞不调节。然而，在这两种情况下，他们调节的PAF的核仁水平。此外，我们发现PAF 49/PAF 53与Pol I的结合受到调节。在检查可能调节这种关联的机制时，我们发现PAF 49在多个位点上被乙酰化。PAF 49的乙酰化状态不影响异源二聚化。然而，hypoacetylated heterodimer binds to Pol I with greater affinity than acetylated heterodimer.此外，我们已经发现异二聚体与Rrn 3相互作用。我们提出了一个模型，其中有一个生化之间的相互作用的Pol I相关的异源二聚体和RRN 3，这种相互作用有利于招聘的RRN 3的聚合酶。由于Rrn 3与Pol I的结合对于酵母和哺乳动物中的转录起始是必不可少的，我们的结果提供了对Rrn 3功能调节的更好理解，并为PAF 49/PAF 53异二聚体在转录起始和Pol I延伸中的作用提供了生物化学基础。
Mammalian PAF49 and PAF53 form a heterodimer and are essential for transcription. However their roles in transcription have not been specifically defined. While the yeast homologues are “not essential” proteins, yeast cells deficient in the homologue of PAF53 grow at 50–66% the wild-type rate at 30 °C, but fail to grow at 25 °C (Liljelund et al., 1992; Beckouet et al., 2008). There is increasing evidence that these proteins may play important roles in transcription initiation and elongation.We have found that while some cells regulated the protein levels of both PAF53 and PAF49, other cells did not. However, in either case they regulated the nucleolar levels of the PAFs. In addition, we found that the association of PAF49/PAF53 with Pol I is regulated. In examining the mechanism that might regulate this association, we have found that PAF49 is acetylated on multiple sites. The acetylation state of PAF49 does not affect heterodimerization. However, hypoacetylated heterodimer binds to Pol I with greater affinity than acetylated heterodimer. Further, we have found that the heterodimer interacts with Rrn3. We propose a model, in which there is a biochemical interaction between the Pol I-associated heterodimer and Rrn3 and that this interaction facilitates the recruitment of Rrn3 to the polymerase. As the binding of Rrn3 to Pol I is essential to transcription initiation in yeast and mammals, our results provide a greater understanding of the regulation of Rrn3 function and provide biochemical underpinning for the roles of the PAF49/PAF53 heterodimer in transcription initiation and elongation by Pol I.