Pin1 modulates RNA polymerase II activity during the transcription cycle.

Pin1 modulates RNA polymerase II activity during the transcription cycle. Research Abstract Details 

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Pin1 modulates RNA polymerase II activity during the transcription cycle. Abstract Text:

Yu-Xin Xu,James L Manley,Yu-Xin Xu,James L Manley,

The C-terminal domain of the RNA polymerase (RNAP) II largest subunit (CTD) plays a critical role in coordinating multiple events in pre-mRNA transcription and processing. Previously we reported that the peptidyl prolyl isomerase Pin1 modulates RNAP II function during the cell cycle. Here we provide evidence that Pin1 affects multiple aspects of RNAP II function via its regulation of CTD phosphorylation. Using chromatin immunoprecipitation (ChIP) assays with CTD phospho-specific antibodies, we confirm that RNAP II displays a dynamic association with specific genes during the cell cycle, preferentially associating with transcribed genes in S phase, while disassociating in M phase in a matter that correlates with changes in CTD phosphorylation. Using inducible Pin1 cell lines, we show that Pin1 overexpression is sufficient to release RNAP II from chromatin, which then accumulates in a hyperphosphorylated form in nuclear speckle-associated structures. In vitro transcription assays show that Pin1 inhibits transcription in nuclear extract, while an inactive Pin1 mutant in fact stimulates it. Several assays indicate that the inhibition largely reflects Pin1 activity during transcription initiation and not elongation, suggesting that Pin1 modulates CTD phosphorylation, and RNAP II activity, during an early stage of the transcription cycle.

Pin1 modulates RNA polymerase II activity during the transcription cycle. Publishing Authors By Initials

YX Xu,JL Manley,YX Xu,JL Manley,

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Pin1 modulates RNA polymerase II activity during the transcription cycle. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Genes & development

VOLUME: 21

Page Numbers: 2950-62

Journal Abbreviation: Genes Dev.

ISSN: 0890-9369

DAY: 15

MONTH: Nov

YEAR: 2007

Pin1 modulates RNA polymerase II activity during the transcription cycle. Information

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LANGUAGE: eng

NlmUniqueID: 8711660

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Grant and Affiliation Information for Pin1 modulates RNA polymerase II activity during the transcription cycle.

AFFILIATION: Department of Biological Sciences, Columbia University, New York, New York 10027, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM37971

ACRONYM: GM

MEDLINETA: Genes Dev

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