TY - JOUR T1 - JMJD6 Cleaves MePCE to Release P-TEFb JF - bioRxiv DO - 10.1101/725853 SP - 725853 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 Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/08/05/725853.abstract N2 - 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. ER -