JMJD6 Cleaves MePCE to Release P-TEFb

Zhang, G.; Lee, S.; Liu, H.; Hill, R.; Hong, X.; Liu, X.; Crawford, F.; Zhang, Q.; Kingsley, M.; Chen, Z.; Lengeling, A.; Bernet, K.; Marrack, P.; Kappler, J.; Hansen, K.; Zhou, Q.; Li, C.-Y.

doi:10.1101/725853

bioRxiv · 10.1101/725853

JMJD6 Cleaves MePCE to Release P-TEFb

Zhang, G.·Lee, S.·Liu, H.·Hill, R.·Hong, X.·Liu, X.·Crawford, F.·Zhang, Q.·Kingsley, M.·Chen, Z.·Lengeling, A.·Bernet, K.·Marrack, P.·Kappler, J.·Hansen, K.·Zhou, Q.·Li, C.-Y.

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Abstract

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.

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Zhang, G., Lee, S., Liu, H., Hill, R., Hong, X., Liu, X., Crawford, F., Zhang, Q., Kingsley, M., Chen, Z., Lengeling, A., Bernet, K., Marrack, P., Kappler, J., Hansen, K., Zhou, Q., Li, C.-Y.. 2019-08-05. JMJD6 Cleaves MePCE to Release P-TEFb. https://doi.org/10.1101/725853

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