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  MYC recruits SPT5 to RNA polymerase II to promote processive transcription elongation.

Baluapuri, A., Hofstetter, J., Dudvarski Stankovic, N., Endres, T., Bhandare, P., Vos, S. M., et al. (2019). MYC recruits SPT5 to RNA polymerase II to promote processive transcription elongation. Molecular Cell, (in press). doi:10.1016/j.molcel.2019.02.031.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-4A4F-3 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-4A55-B
Genre: Journal Article

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 Creators:
Baluapuri, A., Author
Hofstetter, J., Author
Dudvarski Stankovic, N., Author
Endres, T., Author
Bhandare, P., Author
Vos, S. M.1, Author              
Adhikari, B., Author
Schwarz, J. D., Author
Narain, A., Author
Vogt, M., Author
Wang, S. Y., Author
Düster, R., Author
Jung, L. A., Author
Vanselow, J. T., Author
Wiegering, A., Author
Geyer, M., Author
Maric, H. M., Author
Gallant, P., Author
Walz, S., Author
Schlosser, A., Author
Cramer, P.1, Author              Eilers, M., AuthorWolf, E., Author more..
Affiliations:
1Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1863498              

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Free keywords: MYC; RNA polymerase II; SPT5; SPT6; SUPT5H; directionality; elongation rate; processivity; transcription; tumorigenesis
 Abstract: 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.

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Language(s): eng - English
 Dates: 2019-03-27
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.molcel.2019.02.031
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Title: Molecular Cell
Source Genre: Journal
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Pages: - Volume / Issue: - Sequence Number: (in press) Start / End Page: - Identifier: -