General repression of RNA polymerase III transcription is triggered by protein phosphatase type 2A-mediated dephosphorylation of Maf1
General repression of RNA polymerase III transcription is triggered by protein phosphatase type 2A-mediated dephosphorylation of Maf1
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DOI：
10.1016/j.molcel.2006.04.008
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发表时间：
2006-06-09
期刊：
影响因子：
16
通讯作者：
Lefebvre, Olivier
中科院分区：
文献类型：
--
作者：
Oficjalska-Pham, Danuta;Harismendy, Olivier;Lefebvre, Olivier
我们报告的全基因组分析，建立Maf 1作为一个通用的和直接的阻遏酵母RNA聚合酶（Pol）III转录。染色质免疫沉淀（ChIP）耦合微阵列杂交实验表明，Maf 1的抑制条件下（雷帕霉素治疗）与Brf 1和Pol III的解离相关的Pol III转录基因的关联增加。Maf 1可以以各种磷酸化状态存在，并在去磷酸化状态下与Pol III相互作用。Pol III的最大亚基C160被鉴定为Maf 1的靶标。在抑制条件下，Maf 1被去磷酸化并在细胞核中积累，并且Pol III-Maf 1相互作用增加。蛋白磷酸酶2A型（PP 2A）催化亚基编码基因的突变阻止了雷帕霉素诱导的Maf 1去磷酸化，其核积累和抑制Pol III转录。结果表明，Pol III转录可以通过去磷酸化和一般负辅因子的重新定位而全面且快速地下调。
We report genome-wide analyses that establish Maf1 as a general and direct repressor of yeast RNA polymerase (Pol) III transcription. Chromatin immunoprecipitation (ChIP) coupled to microarray hybridization experiments showed an increased association of Maf1 to Pol III-transcribed genes under repressing condition (rapamycin treatment) correlated with a dissociation of Brf1 and Pol III. Maf1 can exist in various phosphorylation states and interacts with Pol III in a dephosphorylated state. The largest subunit of Pol III, C160, was identified as a target of Maf1. Under repressing conditions, Maf1 is dephosphorylated and accumulates in the nucleus, and Pol III-Maf1 interaction increases. Mutations in protein phosphatase type 2A (PP2A) catalytic subunit-encoding genes prevented rapamycin-induced Maf1 dephosphorylation, its nuclear accumulation, and repression of Pol III transcription. The results indicate that Pol III transcription can be globally and rapidly downregulated via dephosphorylation and relocation of a general negative cofactor.