BLAŽEK, Dalibor, Matjaz BARBORIC, Jiří KOHOUTEK, Irena OVEN and B Matija PETERLIN. Oligomerization of HEXIM1 via 7SK snRNA and coiled-coil region directs the inhibition of P-TEFb. Nucleic Acids Research. Oxford, UK: Oxford Press, 2005, vol. 33, No 22, p. 7000-7010. ISSN 0305-1048. Available from: https://dx.doi.org/10.1093/nar/gki997.
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Original name Oligomerization of HEXIM1 via 7SK snRNA and coiled-coil region directs the inhibition of P-TEFb
Authors BLAŽEK, Dalibor, Matjaz BARBORIC, Jiří KOHOUTEK, Irena OVEN and B Matija PETERLIN.
Edition Nucleic Acids Research, Oxford, UK, Oxford Press, 2005, 0305-1048.
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: 7.552
Doi http://dx.doi.org/10.1093/nar/gki997
UT WoS 000234436200015
Keywords in English RNA-POLYMERASE-II; ELONGATION-FACTOR-B; ENERGY-TRANSFER MICROSCOPY; SMOOTH-MUSCLE-CELLS; POSITIVE TRANSCRIPTION; GENE-EXPRESSION; BINDING DOMAIN; HIGH-AFFINITY; LIVING CELLS; CYCLIN T1
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Changed by Changed by: Olga Křížová, učo 56639. Changed: 23/7/2012 07:59.
Abstract
Transcriptional elongation of most eukaryotic genes by RNA polymerase II requires the kinase activity of the positive transcription elongation factor b (P-TEFb). The catalytically active P-TEFb complex becomes inactive when sequestered into the large complex by the cooperative actions of 7SK snRNA and HEXIM1. In this study, we report that HEXIM1 forms oligomers in cells. This oligomerization is mediated by its predicted coiled-coil region in the C-terminal domain and 7SK snRNA that binds a basic region within the central part of HEXIM1. Alanine-mutagenesis of evolutionary conserved leucines in the coiled-coil region and the digestion of 7SK snRNA by RNase A treatment prevent this oligomerization. Importantly, mutations of the N-terminal part of the coiled-coil region abrogate the ability of HEXIM1 to bind and inhibit P-TEFb. Finally, the formation of HEXIM1 oligomers via the C-terminal part of the coiled-coil or basic regions is critical for the inhibition of transcription. Our results suggest that two independent regions in HEXIM1 form oligomers to incorporate P-TEFb into the large complex and determine the inhibition of transcriptional elongation.
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