MYC Recruits SPT5 to RNA Polymerase II to Promote Processive Transcription Elongation
MYC Recruits SPT5 to RNA Polymerase II to Promote Processive Transcription Elongation
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DOI：
10.1016/j.molcel.2019.02.031
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发表时间：
2019-05-16
期刊：
影响因子：
16
通讯作者：
Wolf, Elmar
中科院分区：
文献类型：
--
作者：
Baluapuri, Apoorva;Hofstetter, Julia;Wolf, Elmar
MYC癌蛋白与几乎所有转录基因的启动子近端区域结合，并增强RNA聚合酶II（Pol II）的功能，但其确切的作用模式知之甚少。使用MYC和Pol II复合物的质谱分析，我们在这里显示MYC控制Pol II与一小组转录延伸因子的组装，所述转录延伸因子包括延伸因子DSIF的亚基SPT 5。MYC直接结合SPT5，将SPT5募集到启动子上，并使SPT5能够依赖于CDK7转移到Pol II上。与SPT5的已知功能一致，MYC是快速和进行性转录延伸所必需的。有趣的是，在肿瘤中表达的高水平MYC将SPT 5隔离成非功能性复合物，从而降低生长抑制基因的表达。总之，这些结果表明，MYC控制生产组装的进行性Pol II延伸复合物，并提供洞察致癌水平的MYC如何允许不受控制的细胞生长。
The MYC oncoprotein binds to promoter-proximal regions of virtually all transcribed genes and enhances RNA polymerase II (Pol II) function, but its precise mode of action is poorly understood. Using mass spectrometry of both MYC and Pol II complexes, we show here that MYC controls the assembly of Pol II with a small set of transcription elongation factors that includes SPT5, a subunit of the elongation factor DSIF. MYC directly binds SPT5, recruits SPT5 to promoters, and enables the CDK7-dependent transfer of SPT5 onto Pol II. Consistent with known functions of SPT5, MYC is required for fast and processive transcription elongation. Intriguingly, the high levels of MYC that are expressed in tumors sequester SPT5 into non-functional complexes, thereby decreasing the expression of growth-suppressive genes. Altogether, these results argue that MYC controls the productive assembly of processive Pol II elongation complexes and provide insight into how oncogenic levels of MYC permit uncontrolled cellular growth.