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 a 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, roč. 24, č. 24, s. 4291-4303. ISSN 0261-4189. doi:10.1038/sj.emboj.7600883. 2005.

Základní údaje

• Originální název: Interplay between 7SK snRNA and oppositely charged regions in HEXIM1 direct the inhibition of P-TEFb
• Autoři: BARBORIC, Matjaz, Jiří KOHOUTEK, Jason P PRICE, Dalibor BLAŽEK, David H PRICE a B Matija PETERLIN.
• Vydání: EMBO Journal, NEW YORK, NATURE PUBLISHING GROUP, 2005, 0261-4189.

Další údaje

• Originální jazyk: angličtina
• Typ výsledku: Článek v odborném periodiku
• Obor: 10600 1.6 Biological sciences
• Stát vydavatele: Spojené státy
• Utajení: není předmětem státního či obchodního tajemství
• WWW: URL
• Impakt faktor: Impact factor: 10.053
• Doi: http://dx.doi.org/10.1038/sj.emboj.7600883
• UT WoS: 000234805100008
• Klíčová slova anglicky: HEXIM1; nuclear speckles; P-TEFb; transcription elongation; 7SK snRNA
• Štítky: ok
• Příznaky: Mezinárodní význam, Recenzováno

Anotace

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.