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JMJD6 cleaves MePCE to release positive transcription elongation factor b (P-TEFb) in higher eukaryotes.

Publication ,  Journal Article
Lee, S; Liu, H; Hill, R; Chen, C; Hong, X; Crawford, F; Kingsley, M; Zhang, Q; Liu, X; Chen, Z; Lengeling, A; Bernt, KM; Marrack, P; Zhou, Q ...
Published in: Elife
February 12, 2020

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 b (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 utilize mouse and human models to 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.

Duke Scholars

Published In

Elife

DOI

EISSN

2050-084X

Publication Date

February 12, 2020

Volume

9

Location

England

Related Subject Headings

  • Receptors, Cell Surface
  • RNA Polymerase II
  • Protein Structure, Tertiary
  • Positive Transcriptional Elongation Factor B
  • Mice
  • Methyltransferases
  • Mass Spectrometry
  • Gene Knockout Techniques
  • Blotting, Western
  • Binding Sites
 

Citation

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Lee, S., Liu, H., Hill, R., Chen, C., Hong, X., Crawford, F., … Zhang, G. (2020). JMJD6 cleaves MePCE to release positive transcription elongation factor b (P-TEFb) in higher eukaryotes. Elife, 9. https://doi.org/10.7554/eLife.53930
Lee, Schuyler, Haolin Liu, Ryan Hill, Chunjing Chen, Xia Hong, Fran Crawford, Molly Kingsley, et al. “JMJD6 cleaves MePCE to release positive transcription elongation factor b (P-TEFb) in higher eukaryotes.Elife 9 (February 12, 2020). https://doi.org/10.7554/eLife.53930.
Lee S, Liu H, Hill R, Chen C, Hong X, Crawford F, et al. JMJD6 cleaves MePCE to release positive transcription elongation factor b (P-TEFb) in higher eukaryotes. Elife. 2020 Feb 12;9.
Lee, Schuyler, et al. “JMJD6 cleaves MePCE to release positive transcription elongation factor b (P-TEFb) in higher eukaryotes.Elife, vol. 9, Feb. 2020. Pubmed, doi:10.7554/eLife.53930.
Lee S, Liu H, Hill R, Chen C, Hong X, Crawford F, Kingsley M, Zhang Q, Liu X, Chen Z, Lengeling A, Bernt KM, Marrack P, Kappler J, Zhou Q, Li C-Y, Xue Y, Hansen K, Zhang G. JMJD6 cleaves MePCE to release positive transcription elongation factor b (P-TEFb) in higher eukaryotes. Elife. 2020 Feb 12;9.

Published In

Elife

DOI

EISSN

2050-084X

Publication Date

February 12, 2020

Volume

9

Location

England

Related Subject Headings

  • Receptors, Cell Surface
  • RNA Polymerase II
  • Protein Structure, Tertiary
  • Positive Transcriptional Elongation Factor B
  • Mice
  • Methyltransferases
  • Mass Spectrometry
  • Gene Knockout Techniques
  • Blotting, Western
  • Binding Sites