MYC Recruits SPT5 to RNA Polymerase II to Promote Processive Transcription Elongation
Open accessAbstract
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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Factors regulating RNA Pol II velocity play an essential role in cells.
“Factors regulating RNA Pol II velocity therefore play an essential role in cells and are the topic of several recent studies using genome‐wide RNA Pol II speed measurement methods (Table 2) (Saponaro et al, 2014; Liang et al, 2018; Baluapuri et al, 2019; Cortazar et al, 2019; Gregersen et al, 2019; Hou et al, 2019; Sheridan et al, 2019; Fan et al, 2020).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Baluapuri et al, 2019
MYC is required for fast transcription elongation.
“Moreover, the transcription factor MYC, which directly binds to Spt5 and recruits it to promoters, allowing Spt5 transfer onto RNA Pol II (Baluapuri et al, 2019), has been shown to be required for fast transcription elongation (Liang et al, 2018; Baluapuri et al, 2019; Caggiano et al, 2019).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Baluapuri et al, 2019
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References 72 · Cited by 138
- Authors
- Baluapuri, A., Hofstetter, J., Dudvarski Stankovic, N., Endres, T., Bhandare, P., Vos, S. M., Adhikari, B., Schwarz, J. D., Narain, A., Vogt, M., Wang, S.-Y., Düster, R., Jung, L. A., Vanselow, J. T., Wiegering, A., Geyer, M., Maric, H. M., Gallant, P., Walz, S., Schlosser, A., Cramer, P., Eilers, M., & Wolf, E.
- Affiliations
- University of Würzburg (DE)
- Max Planck Institute for Biophysical Chemistry (DE)
- University of Bonn (DE)
- Karolinska Institutet (SE)
- Corresponding author
- Wolf, Elmar
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 74
- Issue
- 4
- Pages
- 674-687.e11
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC6527870
- OpenAlex
- W2923931114
- Cited by
- 138
- References
- 72
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 28 · 2023: 22 · 2022: 16 · 2021: 23 · 2020: 17 · 2019: 5
- FWCI
- 5.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Online Publication Service of Würzburg University (Würzburg University) (submittedVersion, cc-by)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- Joachim Herz Foundation
- German Excellence Initiative
- German Research Foundation (WO 2108/1-1)
- European Research Council (AuroMYC, TarMYC)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- c-Myc, Spt5, RNA polymerase II, transcription elongation, DSIF, CDK7, oncogenic transcription, tumor growth
- MeSH terms
- Cyclin-Dependent Kinase-Activating Kinase, Humans, Neoplasms, Nuclear Proteins, Promoter Regions, Genetic, RNA Polymerase II, Transcription, Genetic, Proto-Oncogene Proteins c-myc, Cyclin-Dependent Kinases, Transcriptional Elongation Factors, Cell Line, Tumor, Cell Proliferation, Histone Chaperones
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