Abstract

Alternative pre-mRNA splicing contributes significantly to genetic diversity in vertebrates. This proposal is aimed at understanding the mechanisms underlying the regulation of alternative pre-mRNA splicing. Alternatively spliced regions of a pre-mRNA are characterized by the presence of splicing enhancer or silencer sequence elements recognized by splicing factors. Our work concentrates on four systems of pre-mRNA splicing that involve different types of regulatory elements and splicing factors. Included in the RNA regulatory sequence elements to be studied are: 1) C/A-rich exon enhancers that stimulate exon inclusion, G/A-rich exon enhancers that stimulate exon inclusion and regulate 5' splice site usage, G-rich intron enhancers that regulate 5' splice site usage, and C-rich intron elements that stimulate splicing and spliceosome assembly. Experiments are described to: 1) continue characterization of the factors that recognize these RNA elements, 2) identify and characterize factors that recognize element-binding factors to regulate splicing, 3) determine the role of RNA helicases in alternative splicing and 4) investigate the hypothesis that alternative splicing and transcriptional elongation are linked.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM038526-15
Application #
6613433
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Rhoades, Marcus M
Project Start
1988-04-01
Project End
2006-07-31
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
15
Fiscal Year
2003
Total Cost
$489,247
Indirect Cost

  Institution

Name
Baylor College of Medicine
Department
Biochemistry
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Auboeuf, Didier; Dowhan, Dennis H; Dutertre, Martin et al. (2005) A subset of nuclear receptor coregulators act as coupling proteins during synthesis and maturation of RNA transcripts. Mol Cell Biol 25:5307-16
Dowhan, Dennis H; Hong, Eugene P; Auboeuf, Didier et al. (2005) Steroid hormone receptor coactivation and alternative RNA splicing by U2AF65-related proteins CAPERalpha and CAPERbeta. Mol Cell 17:429-39
Auboeuf, Didier; Dowhan, Dennis H; Li, Xiaotao et al. (2004) CoAA, a nuclear receptor coactivator protein at the interface of transcriptional coactivation and RNA splicing. Mol Cell Biol 24:442-53
Auboeuf, Didier; Dowhan, Dennis H; Kang, Yun Kyoung et al. (2004) Differential recruitment of nuclear receptor coactivators may determine alternative RNA splice site choice in target genes. Proc Natl Acad Sci U S A 101:2270-4
Auboeuf, Didier; Honig, Arnd; Berget, Susan M et al. (2002) Coordinate regulation of transcription and splicing by steroid receptor coregulators. Science 298:416-9
Honig, Arnd; Auboeuf, Didier; Parker, Marjorie M et al. (2002) Regulation of alternative splicing by the ATP-dependent DEAD-box RNA helicase p72. Mol Cell Biol 22:5698-707
Stickeler, E; Fraser, S D; Honig, A et al. (2001) The RNA binding protein YB-1 binds A/C-rich exon enhancers and stimulates splicing of the CD44 alternative exon v4. EMBO J 20:3821-30
Grossie Jr, V B (2001) Influence of the ward colon tumor on the innate and endotoxin-induced inflammatory response of the rat. Cancer Invest 19:698-705
Zeng, C; Berget, S M (2000) Participation of the C-terminal domain of RNA polymerase II in exon definition during pre-mRNA splicing. Mol Cell Biol 20:8290-301
McCullough, A J; Berget, S M (2000) An intronic splicing enhancer binds U1 snRNPs to enhance splicing and select 5' splice sites. Mol Cell Biol 20:9225-35

Showing the most recent 10 out of 22 publications