@article{a5c98be921244a0e99fdcef54a128730,
title = "SPT5 stabilization of promoter-proximal RNA polymerase II",
abstract = "Based on in vitro studies, it has been demonstrated that the DSIF complex, composed of SPT4 and SPT5, regulates the elongation stage of transcription catalyzed by RNA polymerase II (RNA Pol II). The precise cellular function of SPT5 is not clear, because conventional gene depletion strategies for SPT5 result in loss of cellular viability. Using an acute inducible protein depletion strategy to circumvent this issue, we report that SPT5 loss triggers the ubiquitination and proteasomal degradation of the core RNA Pol II subunit RPB1, a process that we show to be evolutionarily conserved from yeast to human cells. RPB1 degradation requires the E3 ligase Cullin 3, the unfoldase VCP/p97, and a novel form of CDK9 kinase complex. Our study demonstrates that SPT5 stabilizes RNA Pol II specifically at promoter-proximal regions, permitting RNA Pol II release from promoters into gene bodies and providing mechanistic insight into the cellular function of SPT5 in safeguarding accurate gene expression.",
keywords = "CDK9, Cullin 3, NELF, RNA polymerase II, SPT5, VCP, auxin-inducible degron, degradation, elongation, transcription",
author = "Yuki Aoi and Takahashi, {Yoh hei} and Shah, {Avani P.} and Marta Iwanaszko and Rendleman, {Emily J.} and Khan, {Nabiha H.} and Cho, {Byoung Kyu} and Goo, {Young Ah} and Sheetal Ganesan and Kelleher, {Neil L.} and Ali Shilatifard",
note = "Funding Information: We are grateful to Dr. Edwin Smith for discussions and critical reading of the manuscript. We thank the Shilatifard lab members for helpful discussions and support and B. Monroe for illustrations. We thank M. Kanemaki, A. Holland, I. Cheeseman, D. Foltz, and B. Zheng for providing reagents. We thank K. Eagan for advice on TT-seq. Y.A. was supported by the JSPS Research Fellowship for Young Scientists and the Uehara Memorial Foundation Research Fellowship. Proteomics analysis was performed by the Northwestern Proteomics Core Facility, supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center, an instrumentation award ( S10OD025194 ) from the NIH Office of Director , and the National Resource for Translational and Developmental Proteomics supported by P41 GM108569 . The study is supported by funding from National Cancer Institute grant R01CA214035 to A.S. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = nov,
day = "4",
doi = "10.1016/j.molcel.2021.08.006",
language = "English (US)",
volume = "81",
pages = "4413--4424.e5",
journal = "Molecular cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "21",
}