DOI: 10.1101/gad.1135503. Pin1 modulates the structure and function of human RNA polymerase II

Pin1 modulates the structure and function of human RNA polymerase II

10.1101/gad.1135503

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

The C-terminal domain of the RNA polymerase (RNAP) II largest subunit (CTD) plays critical roles both in transcription of mRNA precursors and in the processing reactions needed to form mature mRNAs. The CTD undergoes dynamic changes in phosphorylation during the transcription cycle, and this plays a significant role in coordinating its multiple activities. But how these changes themselves are regulated is not well understood. Here we show that the peptidyl-prolyl isomerase Pin1 influences the phosphorylation status of the CTD in vitro by inhibiting the CTD phosphatase FCP1 and stimulating CTD phosphorylation by cdc2/cyclin B. This is reflected in vivo by accumulation of hypophosphorylated RNAP II in pin1-/- cells, and of a novel hyper-hyperphosphorylated form in cells induced to overexpress Pin1. This hyper-hyperphosphorylated form of RNAP II also accumulates in M-phase cells, in a Pin1-dependent manner, and associates specifically with Pin1. Functionally, we find that Pin1 overexpression specifically inhibits ongoing transcription of mRNA precursors in vivo and both transcription and RNAP II-stimulated pre-mRNA splicing in cell extracts. Pin1 thus plays a significant role in regulating RNAP II CTD structure and function.

Bibliography

Xu, Y.-X., Hirose, Y., Zhou, X. Z., Lu, K. P., & Manley, J. L. (2003). Pin1 modulates the structure and function of human RNA polymerase II. Genes & Development, 17(22), 2765â2776.

Authors 5

Yu-Xin Xu (first)
Yutaka Hirose (additional)
Xiao Zhen Zhou (additional)
Kun Ping Lu (additional)
James L. Manley (additional)

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Dates

Type	When
Created	21 years, 9 months ago (Nov. 10, 2003, 8:12 p.m.)
Deposited	3 years, 9 months ago (Nov. 15, 2021, 10:35 p.m.)
Indexed	1 month, 3 weeks ago (July 2, 2025, 2:31 p.m.)
Issued	22 years, 7 months ago (Jan. 1, 2003)
Published	22 years, 7 months ago (Jan. 1, 2003)
Published Online	22 years, 7 months ago (Jan. 1, 2003)
Published Print	21 years, 9 months ago (Nov. 15, 2003)

Funders 0

None

BibTeX

@article{Xu_2003, title={Pin1 modulates the structure and function of human RNA polymerase II}, volume={17}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.1135503}, DOI={10.1101/gad.1135503}, number={22}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Xu, Yu-Xin and Hirose, Yutaka and Zhou, Xiao Zhen and Lu, Kun Ping and Manley, James L.}, year={2003}, month=jan, pages={2765–2776} }

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