MYC Recruits SPT5 to RNA Polymerase II to Promote Processive Transcription Elongation
| Autor: | Robert Düster, Martin Eilers, Bikash Adhikari, Shuang-Yan Wang, Ashwin Narain, Elmar Wolf, Susanne Walz, Armin Wiegering, Peter Gallant, Patrick Cramer, Pranjali Bhandare, Andreas Schlosser, Seychelle M. Vos, Julia Hofstetter, Theresa Endres, Apoorva Baluapuri, Hans Michael Maric, Nevenka Dudvarski Stankovic, Matthias Geyer, Jens T. Vanselow, Jessica Denise Schwarz, Lisa Anna Jung, Markus Vogt |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Transcription
Genetic Protein subunit RNA polymerase II MYC Article elongation rate Proto-Oncogene Proteins c-myc 03 medical and health sciences directionality 0302 clinical medicine Transcription (biology) Cell Line Tumor Neoplasms Humans Histone Chaperones Promoter Regions Genetic Molecular Biology Gene Cell Proliferation 030304 developmental biology 0303 health sciences biology Nuclear Proteins Promoter Cell Biology Processivity processivity DSIF Cyclin-Dependent Kinases SUPT5H Cell biology SPT6 Elongation factor tumorigenesis biology.protein Transcriptional Elongation Factors transcription Cyclin-Dependent Kinase-Activating Kinase 030217 neurology & neurosurgery SPT5 |
| Zdroj: | Molecular Cell |
| ISSN: | 1097-2765 |
| Popis: | Summary 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. Graphical Abstract Highlights • MYC enhances productive transcription by defining the protein composition of Pol II • MYC directly binds SPT5 and hands it over to Pol II in a CDK7-dependent manner • Transfer of SPT5 increases speed and processivity of Pol II • MYC’s effects on Pol II function shape its tumor-specific gene expression profile Baluapuri et al. report that MYC governs transition of Pol II into a transcriptionally engaged form by loading the SPT5 protein onto it. This increases Pol II processivity and productive transcription. The effect of MYC on Pol II can regulate expression of those genes, which help tumors to grow. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|