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

TY - JOUR

T1 - A 5' splice site enhances the recruitment of basal transcription initiation factors in vivo

AU - Damgaard, Christian Kroun

AU - Kahns, Søren

AU - Lykke-Andersen, Søren

AU - Nielsen, Anders Lade

AU - Jensen, Torben Heick

AU - Kjems, Jørgen

PY - 2008/2/1

Y1 - 2008/2/1

N2 - 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 TFIID, TFIIB, and TFIIH on a gene containing a functional 5' splice site. In addition to their promoter association, the TFIID 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 pre-initiation complex assembly.

AB - 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 TFIID, TFIIB, and TFIIH on a gene containing a functional 5' splice site. In addition to their promoter association, the TFIID 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 pre-initiation complex assembly.

KW - Cell Line

KW - Globins/biosynthesis

KW - HIV-1/genetics

KW - Humans

KW - Multiprotein Complexes/genetics

KW - Mutation

KW - Promoter Regions, Genetic/physiology

KW - RNA Splice Sites/physiology

KW - RNA Splicing/physiology

KW - RNA, Small Nuclear/genetics

KW - Transcription Factors/genetics

KW - Transcription, Genetic/physiology

U2 - 10.1016/j.molcel.2007.11.035

DO - 10.1016/j.molcel.2007.11.035

M3 - Journal article

C2 - 18243121

SN - 1097-2765

VL - 29

SP - 271

EP - 278

JO - Molecular Cell

JF - Molecular Cell

IS - 2

ER -