The majority of eukaryotic genes contain introns, which are removed from the RNA polymerase II transcribed pre-messenger RNA by the splice some, to produce a mature mRNA. Defects in both pre-mRNA splicing and histone modifications have been implicated in human disease. Although transcription and RNA splicing have been studied as biochemical separate reactions, recent studies indicate that splicing occur co-transcription ally. Since co-transcriptional splicing occurs in the context of a chromatin, based upon our preliminary results, we are exploring how U2 snRNP proteins interact with the histone acetyltransferase, Gcn5 to coordinate transcription and pre-mRNA splicing. Using ChIP, we will examine how deletion of Gcn5 affects splicesome assembly. In addition, we will examine histone H3 acetylation and Gcn5 association to intronless and intron-containing genes when splicing factors are deleted. These finding will help us better understand the mechanism of the relationship between transcription and splicing as it relates to gene expression. Understanding these mechanisms will help us comprehend the origin of human disease and unveil possible new targets for the development of novel treatments for human disease. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31GM078745-03
Application #
7470030
Study Section
Minority Programs Review Committee (MPRC)
Program Officer
Gaillard, Shawn R
Project Start
2006-09-01
Project End
2009-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
3
Fiscal Year
2008
Total Cost
$29,923
Indirect Cost
Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Gunderson, Felizza Q; Merkhofer, Evan C; Johnson, Tracy L (2011) Dynamic histone acetylation is critical for cotranscriptional spliceosome assembly and spliceosomal rearrangements. Proc Natl Acad Sci U S A 108:2004-9
Gunderson, Felizza Q; Johnson, Tracy L (2009) Acetylation by the transcriptional coactivator Gcn5 plays a novel role in co-transcriptional spliceosome assembly. PLoS Genet 5:e1000682