A 5′ splice site enhances the recruitment of basal transcription initiation factors in vivo

被引:132
作者
Damgaard, Christian Kroun [1 ,2 ]
Kahns, Soren [3 ]
Lykke-Andersen, Soren [1 ,2 ]
Nielsen, Anders Lade [3 ]
Jensen, Torben Heick [1 ,2 ]
Kjems, Jorgen [2 ]
机构
[1] Aarhus Univ, Ctr mRNP Biogenesis & Metab, DK-8000 Aarhus, Denmark
[2] Aarhus Univ, Dept Mol Biol, DK-8000 Aarhus, Denmark
[3] Aarhus Univ, Dept Human Genet, DK-8000 Aarhus, Denmark
关键词
D O I
10.1016/j.molcel.2007.11.035
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Transcription and pre-mRNA splicing are interdependent events. Although mechanisms governing the effects of transcription on splicing are becoming increasingly clear, the means by which splicing affects transcription remain elusive. Using cell lines stably expressing HIV-1 or beta-globin mRNAs, harboring wild-type or various 5' splice site mutations, we demonstrate a strong positive correlation between splicing efficiency and transcription activity. Interestingly, a 5' splice site can stimulate transcription even in the absence of splicing. Chromatin immunoprecipitation experiments show enhanced promoter docking of transcription initiation factors TRID, TFIIB, and TFIIH on a gene containing a functional 5' splice site. In addition to their promoter association, the TRID and TFIIH components, TBP and p89, are specifically recruited to the 5' splice site region. Our data suggest a model in which a promoter-proximal 5' splice site via its U1 snRNA interaction can feed back to stimulate transcription initiation by enhancing preinitiation complex assembly.
引用
收藏
页码:271 / 278
页数:8
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