Phosphorylated MED1 links transcription recycling and cancer growth

Zhong Chen, Zhenqing Ye, Raymond E. Soccio, Tomoyoshi Nakadai, William Hankey, Yue Zhao, Furong Huang, Fuwen Yuan, Hongyan Wang, Zhifen Cui, Benjamin Sunkel, Dayong Wu, Richard K. Dzeng, Jennifer M. Thomas-Ahner, Tim H.M. Huang, Steven K. Clinton, Jiaoti Huang, Mitchell A. Lazar, Victor X. Jin, Robert G. RoederQianben Wang

Research output: Contribution to journalArticlepeer-review


Mediator activates RNA polymerase II (Pol II) function during transcription, but it remains unclear whether Mediator is able to travel with Pol II and regulate Pol II transcription beyond the initiation and early elongation steps. By using in vitro and in vivo transcription recycling assays, we find that human Mediator 1 (MED1), when phosphorylated at the mammal-specific threonine 1032 by cyclin-dependent kinase 9 (CDK9), dynamically moves along with Pol II throughout the transcribed genes to drive Pol II recycling after the initial round of transcription. Mechanistically, MED31 mediates the recycling of phosphorylated MED1 and Pol II, enhancing mRNA output during the transcription recycling process. Importantly, MED1 phosphorylation increases during prostate cancer progression to the lethal phase, and pharmacological inhibition of CDK9 decreases prostate tumor growth by decreasing MED1 phosphorylation and Pol II recycling. Our results reveal a novel role of MED1 in Pol II transcription and identify phosphorylated MED1 as a targetable driver of dysregulated Pol II recycling in cancer.

Original languageEnglish (US)
Pages (from-to)4450-4463
Number of pages14
JournalNucleic acids research
Issue number8
StatePublished - May 6 2022

ASJC Scopus subject areas

  • Genetics


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