PT  - JOURNAL ARTICLE
AU  - Schuyler Lee
AU  - Haolin Liu
AU  - Ryan Hill
AU  - Xia Hong
AU  - Xinjian Liu
AU  - Fran Crawford
AU  - Qianqian Zhang
AU  - Molly Kingsley
AU  - Zhongzhou Chen
AU  - Andreas Lengeling
AU  - Kathrin Bernet
AU  - Philippa Marrack
AU  - John Kappler
AU  - Kirk Hansen
AU  - Qiang Zhou
AU  - Chuan-Yuan Li
AU  - Gongyi Zhang
TI  - JMJD6 Cleaves MePCE to Release P-TEFb
AID  - 10.1101/725853
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 725853
4099  - http://biorxiv.org/content/early/2019/08/05/725853.short
4100  - http://biorxiv.org/content/early/2019/08/05/725853.full
AB  - More than 30% of genes in higher eukaryotes are regulated by promoter-proximal pausing of RNA polymerase II (Pol II). Phosphorylation of Pol II-CTD by positive transcription elongation factor (P-TEFb) is a necessary precursor event that enables productive transcription elongation. The exact mechanism on how the sequestered P-TEFb is released from the 7SK snRNP complex and recruited to Pol II-CTD remains unknown. In this report, we reveal methylphosphate capping enzyme (MePCE), a core component of the 7SK snRNP complex, as the cognate substrate for Jumonji domain-containing 6 (JMJD6)’s novel proteolytic function. Our evidences consist of a crystal structure of JMJD6 bound to methyl-arginine, enzymatic assays of JMJD6 cleaving MePCE in vivo and in vitro, binding assays, and downstream effects of Jmjd6 knockout and overexpression on Pol II-CTD phosphorylation. We propose that JMJD6 assists bromodomain containing 4 (BRD4) to recruit P-TEFb to Pol II-CTD by disrupting the 7SK snRNP complex.