Oligomerization of HEXIM1 via 7SK snRNA and coiled-coil region
directs the inhibition of P-TEFb

J 2005

Oligomerization of HEXIM1 via 7SK snRNA and coiled-coil region directs the inhibition of P-TEFb

BLAŽEK, Dalibor, Matjaz BARBORIC, Jiří KOHOUTEK, Irena OVEN, B Matija PETERLIN et. al.

Basic information

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

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

Abstract

V originále

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.

Citovat

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.

@article{987842,
   author = {Blažek, Dalibor and Barboric, Matjaz and Kohoutek, Jiří and Oven, Irena and Peterlin, B Matija},
   article_location = {Oxford, UK},
   article_number = {22},
   doi = {http://dx.doi.org/10.1093/nar/gki997},
   keywords = {RNA-POLYMERASE-II; ELONGATION-FACTOR-B; ENERGY-TRANSFER MICROSCOPY; SMOOTH-MUSCLE-CELLS; POSITIVE TRANSCRIPTION; GENE-EXPRESSION; BINDING DOMAIN; HIGH-AFFINITY; LIVING CELLS; CYCLIN T1},
   language = {eng},
   issn = {0305-1048},
   journal = {Nucleic Acids Research},
   title = {Oligomerization of HEXIM1 via 7SK snRNA and coiled-coil region directs the inhibition of P-TEFb},
   url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1322273/},
   volume = {33},
   year = {2005}
}

TY  - JOUR
ID  - 987842
AU  - Blažek, Dalibor - Barboric, Matjaz - Kohoutek, Jiří - Oven, Irena - Peterlin, B Matija
PY  - 2005
TI  - Oligomerization of HEXIM1 via 7SK snRNA and coiled-coil region directs the inhibition of P-TEFb
JF  - Nucleic Acids Research
VL  - 33
IS  - 22
SP  - 7000-7010
EP  - 7000-7010
PB  - Oxford Press
SN  - 03051048
KW  - RNA-POLYMERASE-II
KW  - ELONGATION-FACTOR-B
KW  - ENERGY-TRANSFER MICROSCOPY
KW  - SMOOTH-MUSCLE-CELLS
KW  - POSITIVE TRANSCRIPTION
KW  - GENE-EXPRESSION
KW  - BINDING DOMAIN
KW  - HIGH-AFFINITY
KW  - LIVING CELLS
KW  - CYCLIN T1
UR  - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1322273/
N2  - 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.
ER  -

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. \textit{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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