LARP7 is a stable component of the 7SK snRNP while P-TEFb, HEXIM1 and hnRNP A1 are reversibly associated

Brian J Krueger; Célia Jeronimo; Bibhuti Bhusan Roy; Annie Bouchard; Charlotte Barrandon; Sarah A Byers; Courtney E Searcey; Jeffrey J Cooper; Olivier Bensaude; Éric A Cohen; Benoit Coulombe; David H Price

doi:10.1093/nar/gkn061

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LARP7 is a stable component of the 7SK snRNP while P-TEFb, HEXIM1 and hnRNP A1 are reversibly associated

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LARP7 is a stable component of the 7SK snRNP while P-TEFb, HEXIM1 and hnRNP A1 are reversibly associated

Brian J Krueger, Célia Jeronimo, Bibhuti Bhusan Roy, Annie Bouchard, Charlotte Barrandon, Sarah A Byers, Courtney E Searcey, Jeffrey J Cooper, Olivier Bensaude, Éric A Cohen, …

Nucleic acids research, Vol.36(7), pp.2219-2229

04/2008

DOI: 10.1093/nar/gkn061

PMCID: PMC2367717

PMID: 18281698

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Abstract

Regulation of the elongation phase of RNA polymerase II transcription by P-TEFb is a critical control point for gene expression. The activity of P-TEFb is regulated, in part, by reversible association with one of two HEXIMs and the 7SK snRNP. A recent proteomics survey revealed that P-TEFb and the HEXIMs are tightly connected to two previously-uncharacterized proteins, the methyphosphate capping enzyme, MEPCE, and a La-related protein, LARP7. Glycerol gradient sedimentation analysis of lysates from cells treated with P-TEFb inhibitors, suggested that the 7SK snRNP reorganized such that LARP7 and 7SK remained associated after P-TEFb and HEXIM1 were released. Immunodepletion of LARP7 also depleted most of the 7SK regardless of the presence of P-TEFb, HEXIM or hnRNP A1 in the complex. Small interfering RNA knockdown of LARP7 in human cells decreased the steady-state level of 7SK, led to an initial increase in free P-TEFb and increased Tat transactivation of the HIV-1 LTR. Knockdown of LARP7 or 7SK ultimately caused a decrease in total P-TEFb protein levels. Our studies have identified LARP7 as a 7SK-binding protein and suggest that free P-TEFb levels are determined by a balance between release from the large form and reduction of total P-TEFb.

Molecular Biology

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Title: Subtitle: LARP7 is a stable component of the 7SK snRNP while P-TEFb, HEXIM1 and hnRNP A1 are reversibly associated
Creators: Brian J Krueger - Molecular and Cellular Biology Program, University of Iowa, Iowa City, Iowa, USA
Célia Jeronimo - Molecular and Cellular Biology Program, University of Iowa, Iowa City, Iowa, USA
Bibhuti Bhusan Roy - Molecular and Cellular Biology Program, University of Iowa, Iowa City, Iowa, USA
Annie Bouchard - Molecular and Cellular Biology Program, University of Iowa, Iowa City, Iowa, USA
Charlotte Barrandon - Molecular and Cellular Biology Program, University of Iowa, Iowa City, Iowa, USA
Sarah A Byers - Molecular and Cellular Biology Program, University of Iowa, Iowa City, Iowa, USA
Courtney E Searcey - Molecular and Cellular Biology Program, University of Iowa, Iowa City, Iowa, USA
Jeffrey J Cooper - Molecular and Cellular Biology Program, University of Iowa, Iowa City, Iowa, USA
Olivier Bensaude - Molecular and Cellular Biology Program, University of Iowa, Iowa City, Iowa, USA
Éric A Cohen - Molecular and Cellular Biology Program, University of Iowa, Iowa City, Iowa, USA
Benoit Coulombe - Molecular and Cellular Biology Program, University of Iowa, Iowa City, Iowa, USA
David H Price - Molecular and Cellular Biology Program, University of Iowa, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: Nucleic acids research, Vol.36(7), pp.2219-2229
DOI: 10.1093/nar/gkn061
PMID: 18281698
PMCID: PMC2367717
NLM abbreviation: Nucleic Acids Res
ISSN: 0305-1048
eISSN: 1362-4962
Publisher: Oxford University Press
Language: English
Date published: 04/2008
Academic Unit: Biochemistry and Molecular Biology
Record Identifier: 9984024554402771

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