Journal article
Interplay between 7SK snRNA and oppositely charged regions in HEXIM1 direct the inhibition of P-TEFb
The EMBO journal, Vol.24(24), pp.4291-4303
12/21/2005
DOI: 10.1038/sj.emboj.7600883
PMCID: PMC1356324
PMID: 16362050
Abstract
Transcription elongation of eukaryotic genes by RNA polymerase II depends on the positive transcription elongation factor b (P-TEFb). When sequestered into the large complex, P-TEFb kinase activity is inhibited by the coordinate actions of 7SK small nuclear RNA (7SK snRNA) and hexamethylene bisacetamide (HMBA)-induced protein 1 (HEXIM1). We found that the basic region in HEXIM1 directs its nuclear import via two monopartite and two bipartite nuclear localization sequences. Moreover, the arginine-rich motif within it is essential for its binding to 7SK snRNA, P-TEFb, and inhibition of transcription. Notably, the basic region interacts with the adjacent acidic regions in the absence of RNA. The removal of the positive or negative charges from these regions in HEXIM1 leads to its sequestration into the large complex and inhibition of transcription independently of the arginine-rich motif. Finally, the removal of the negative charges from HEXIM1 results in its subnuclear localization into nuclear speckles. We propose a model where the interplay between 7SK snRNA and oppositely charged regions in HEXIM1 direct its binding to P-TEFb and subcellular localization that culminates in the inhibition of transcription.
Details
- Title: Subtitle
- Interplay between 7SK snRNA and oppositely charged regions in HEXIM1 direct the inhibition of P-TEFb
- Creators
- Matjaz Barboric - Departments of Medicine, Microbiology, and Immunology, Rosalind Russell Medical Research Center, University of California at San Francisco, San Francisco, CA, USAJiří Kohoutek - Departments of Medicine, Microbiology, and Immunology, Rosalind Russell Medical Research Center, University of California at San Francisco, San Francisco, CA, USAJason P Price - Department of Biochemistry, University of Iowa, Iowa City, Iowa, USADalibor Blazek - Departments of Medicine, Microbiology, and Immunology, Rosalind Russell Medical Research Center, University of California at San Francisco, San Francisco, CA, USADavid H Price - Department of Biochemistry, University of Iowa, Iowa City, Iowa, USAB Matija Peterlin - Departments of Medicine, Microbiology, and Immunology, Rosalind Russell Medical Research Center, University of California at San Francisco, San Francisco, CA, USA
- Resource Type
- Journal article
- Publication Details
- The EMBO journal, Vol.24(24), pp.4291-4303
- Publisher
- Nature Publishing Group
- DOI
- 10.1038/sj.emboj.7600883
- PMID
- 16362050
- PMCID
- PMC1356324
- ISSN
- 0261-4189
- eISSN
- 1460-2075
- Alternative title
- Charged regions in HEXIM1 direct P-TEFb inhibition
- Language
- English
- Date published
- 12/21/2005
- Academic Unit
- Biochemistry and Molecular Biology
- Record Identifier
- 9984025266402771
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