Interplay between 7SK snRNA and oppositely charged regions in
HEXIM1 direct the inhibition of P-TEFb

J 2005

Interplay between 7SK snRNA and oppositely charged regions in HEXIM1 direct the inhibition of P-TEFb

BARBORIC, Matjaz, Jiří KOHOUTEK, Jason P PRICE, Dalibor BLAŽEK, David H PRICE et. al.

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

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: 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

Abstract

V originále

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.

Citovat

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.

@article{987840,
   author = {Barboric, Matjaz and Kohoutek, Jiří and Price, Jason P and Blažek, Dalibor and Price, David H and Peterlin, B Matija},
   article_location = {NEW YORK},
   article_number = {24},
   doi = {http://dx.doi.org/10.1038/sj.emboj.7600883},
   keywords = {HEXIM1; nuclear speckles; P-TEFb; transcription elongation; 7SK snRNA},
   language = {eng},
   issn = {0261-4189},
   journal = {EMBO Journal},
   title = {Interplay between 7SK snRNA and oppositely charged regions in HEXIM1 direct the inhibition of P-TEFb},
   url = {http://www.nature.com/emboj/journal/v24/n24/pdf/7600883a.pdf},
   volume = {24},
   year = {2005}
}

TY  - JOUR
ID  - 987840
AU  - Barboric, Matjaz - Kohoutek, Jiří - Price, Jason P - Blažek, Dalibor - Price, David H - Peterlin, B Matija
PY  - 2005
TI  - Interplay between 7SK snRNA and oppositely charged regions in HEXIM1 direct the inhibition of P-TEFb
JF  - EMBO Journal
VL  - 24
IS  - 24
SP  - 4291-4303
EP  - 4291-4303
PB  - NATURE PUBLISHING GROUP
SN  - 02614189
KW  - HEXIM1
KW  - nuclear speckles
KW  - P-TEFb
KW  - transcription elongation
KW  - 7SK snRNA
UR  - http://www.nature.com/emboj/journal/v24/n24/pdf/7600883a.pdf
N2  - 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.
ER  -

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. \textit{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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