Phenotypic analysis of Paf1/RNA polymerase II complex mutations reveals connections to cell cycle regulation, protein synthesis, and lipid and nucleic acid metabolism
Phenotypic analysis of Paf1/RNA polymerase II complex mutations reveals connections to cell cycle regulation, protein synthesis, and lipid and nucleic acid metabolism
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DOI：
10.1007/s00438-002-0752-8
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发表时间：
2002-10-01
影响因子：
3.1
通讯作者：
Jaehning, JA
中科院分区：
文献类型：
--
作者：
Betz, JL;Chang, M;Jaehning, JA
Paf1 是酵母中的一种 RNA 聚合酶 II 相关蛋白，它定义了一个与 Srb/Mediator 全酶不同的复合物。 Paf1 复合体还包含 Ctr9、Cdc73、Hpr1、Ccr4、Rtf1 和 Leo1，是部分酵母基因完全表达所必需的，特别是那些对 Pkc1/MAP 激酶级联信号敏感的基因。我们对 Paf1 复合物中存在的因子的缺失突变体的多效性表型进行了广泛的表征，鉴定了十多种新表型，并且在某些情况下，为生长缺陷建立了可能的分子解释。例如，paf1Delta会导致对羟基脲的敏感性；这种表型与 RNR1 转录本丰度的减少相关，并受到 RNR1 过度表达的抑制。相比之下，paf1Delta 细胞对转录延伸抑制剂 6-azauracil 和麦考酚酸的耐药性与其去抑制 IMD2 转录物的能力相关。我们测试了这样的假设：Paf1 通过 DNA 结合因子 Swi4、Mbp1 或 Rlm1 与某些启动子进行通讯。 Paf1 复合体成分的突变表型在 swi4Delta 背景下加剧，表明该复合体的作用途径与 Swi4 控制的途径平行。相反，mbp1Delta 和 rlm1Delta 突变不增强表型的事实表明，Paf1 复合物可能与 Mbp1 和 Rlm1 在相同的调节途径中发挥作用。
Paf1 is an RNA polymerase II-associated protein in yeast, which defines a complex that is distinct from the Srb/Mediator holoenzyme. The Paf1 complex, which also contains Ctr9, Cdc73, Hpr1, Ccr4, Rtf1 and Leo1, is required for full expression of a subset of yeast genes, particularly those responsive to signals from the Pkc1/MAP kinase cascade. We have extensively characterized the pleiotropic phenotypes of deletion mutants for factors present in the Paf1 complex, identifying more than a dozen new phenotypes, and, in some cases, establishing possible molecular explanations for the growth defects. For example, paf1Delta causes sensitivity to hydroxyurea; this phenotype correlates with a reduction in RNR1 transcript abundance and is suppressed by over-expression of RNR1. In contrast, the resistance of paf1Delta cells to the transcription elongation inhibitors 6-azauracil and mycophenolic acid correlates with its ability to derepress the IMD2 transcript. We tested the hypothesis that Paf1 communicates with some promoters through the DNA-binding factors Swi4, Mbp1 or Rlm1. The phenotypes of mutations in Paf1 complex components are exacerbated in the swi4Delta background, suggesting that the complex acts in a pathway parallel to that controlled by Swi4. Conversely, the fact that mbp1Delta and rlm1Delta mutations do not enhance the phenotypes suggests that the Paf1 complex may function in the same regulatory pathway(s) with Mbp1 and Rlm1.