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Cap-binding protein complex links pre-mRNA capping to transcription elongationand alternative splicing through positive transcription elongation factor b (P-TEFb)Lenasi, Tina ; Peterlin, Matija Boris ; Barborič, Matjaž, 1975-Promoter-proximal pausing of RNAPII coincides with the formation of the cap structure at the 5' end of pre-mRNA, which is bound by the cap-binding proteincomplex (CBC). Although the positive ... transcription elongation factor b (P-TEFb) stimulates the release of RNAPII from pausing and promotes transcription elongation and alternative splicing by phosphorylating the RNAPII C-terminal domain at Ser2 (S2-P RNAPII), it is unknown whether CBC facilitates these events. In this study, we report that CBC interacts with P-TEFb and transcriptionally engaged RNAPII and is globally required for optimal levels of S2-P RNAPII. Quantitative nascent RNA immunoprecipitation and ChIP experiments reveal that depletion of CBC attenuates HIV-1 Tat transactivation and impedes transcription elongation of investigated CBC-dependent endogenous genes by decreasing the levels of P-TEFb and S2-P RNAPII, leading to accumulation of RNAPII in the body of these genes. Finally,CBC is essential for the promotion of alternative splicing through facilitating P-TEFb, S2-P RNAPII, and splicing factor 2/alternative splicing factor occupancy at a splicing minigene. These findings disclose a vital role of CBC in connecting pre-mRNA capping to transcription elongation and alternative splicing via P-TEFb.Source: The Journal of biological chemistry. - ISSN 0021-9258 (Vol. 286, issue 26, 2011, str. 22758-22768)Type of material - article, component partPublish date - 2011Language - englishCOBISS.SI-ID - 29173209
Author
Lenasi, Tina |
Peterlin, Matija Boris |
Barborič, Matjaž, 1975-
Topics
Alternative Splicing |
Physiology |
Hela Cells |
Rna Polymerase Ii |
Genetics |
Metabolism |
Rna Precursors |
Biosynthesis |
Genetics |
Transcription, Genetic |
Physiology |
Alternativno spajanje |
Transkripcija genetična |
RNA polimeraza II |
RNA, predstopnje |
Hela celice
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Lenasi, Tina | 19330 |
Peterlin, Matija Boris | 34721 |
Barborič, Matjaž, 1975- | 20346 |
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