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@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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