The F box protein Dsg1/Mdm30 is a transcriptional coactivator that stimulates Gal4 turnover and cotranscriptional mRNA processing
The F box protein Dsg1/Mdm30 is a transcriptional coactivator that stimulates Gal4 turnover and cotranscriptional mRNA processing
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DOI：
10.1016/j.cell.2004.12.025
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发表时间：
2005-03-25
期刊：
影响因子：
64.5
通讯作者：
Tansey, WR
中科院分区：
文献类型：
--
作者：
Muratani, M;Kung, C;Tansey, WR
我们在这里报道了典型的酵母转录因子Gal4经历了两种不同的泛素介导的蛋白分解模式：一种独立于转录并限制Gal4的功能，另一种是转录偶联的，对Gal4靶基因的有效激活是必不可少的。转录活性Gal4的破坏依赖于一种名为DSGL/MDM30的F盒蛋白。在没有DSG1的情况下，Gal4是稳定的，非泛素化的，不能有效地刺激转录。对DSGL-NuIL酵母的表型分析表明，Gal基因RNA和蛋白质水平之间存在显著的脱节；在缺乏DSGL的情况下，Gal4靶基因被转录，但所产生的RNA不被翻译。这些RNA的翻译缺陷与RNA聚合酶11羧基末端结构域的磷酸化缺陷有关，这反过来又影响RNA加工机制的招募。我们认为Gal4泛素化和破坏是启动能力强的转录复合体转变为能够适当处理mRNA的完全成熟的伸长复合体所必需的。
We report here that the prototypical yeast transcription factor Gal4 undergoes two distinct modes of ubiquitin-mediated proteolysis: one that occurs independent of transcription and restricts Gal4 function, and another that is transcription coupled and essential for productive activation of Gal4 target genes. Destruction of transcriptionally active Gal4 depends on an F box protein called Dsgl/Mdm30. In the absence of Dsg1, Gal4 is stable, nonubiquitylated, and unable to productively stimulate transcription. Analysis of the phenotype of dsgl-nuil yeast reveals a striking disconnect between GAL gene RNA and protein levels; in the absence of Dsgl, Gal4 target genes are transcribed, but the resulting RNAs are not translated. The translational defects of these RNAs are related to defects in phosphorylation of the RNA polymerase 11 carboxy-terminal domain, which in turn affects recruitment of RNA processing machinery. We propose that Gal4 ubiquitylation and destruction are required for initiation-competent transcription complexes to transition to fully mature elongating complexes capable of appropriate mRNA processing.