BARBORIC, Matjaz, Jiří KOHOUTEK, Jason P PRICE, Dalibor BLAŽEK, David H PRICE and B Matija PETERLIN. Interplay between 7SK snRNA and oppositely charged regions in HEXIM1 direct the inhibition of P-TEFb. EMBO Journal. NEW YORK: NATURE PUBLISHING GROUP, 2005, vol. 24, No 24, p. 4291-4303. ISSN 0261-4189. Available from: https://dx.doi.org/10.1038/sj.emboj.7600883.
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Basic information
Original name Interplay between 7SK snRNA and oppositely charged regions in HEXIM1 direct the inhibition of P-TEFb
Authors BARBORIC, Matjaz, Jiří KOHOUTEK, Jason P PRICE, Dalibor BLAŽEK, David H PRICE and B Matija PETERLIN.
Edition EMBO Journal, NEW YORK, NATURE PUBLISHING GROUP, 2005, 0261-4189.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10600 1.6 Biological sciences
Country of publisher United States of America
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 10.053
Doi http://dx.doi.org/10.1038/sj.emboj.7600883
UT WoS 000234805100008
Keywords in English HEXIM1; nuclear speckles; P-TEFb; transcription elongation; 7SK snRNA
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Tags International impact, Reviewed
Changed by Changed by: Olga Křížová, učo 56639. Changed: 23/7/2012 06:15.
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.
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