INVITED AND SPECIAL SESSIONS
Thursday, October 27
11:00 AM-1:00 PM
Concurrent Invited Sessions II (26-32)
SESSION 30 - The Spliceosome and Human Disease
Ballroom A-D
Co-Moderators: Douglas Marchuk, Duke University Medical Center, Durham, NC; and Susan A. Slaugenhaupt, Massachusetts General Hospital and Harvard Medical School, Boston
The splicing of messenger RNA is a complex cellular process that results in the joining of exons and the removal of introns. Splicing is accomplished by the spliceosome, which consists of 5 snRNPs and over 100 other proteins. The completion of the human genome sequence, and the resulting estimate of only 27,000 genes, clearly demonstrates a major role for alternative splicing in generating protein diversity. It is not surprising, therefore, that approximately 15% of all mutations that cause human genetic disease result from defective splicing of pre-mRNA. Increasingly, previously reported missense mutations or even apparently silent polymorphisms have been shown to alter pre-mRNA splicing patterns that can lead to disease. Recent studies have shown that most exons contain exonic splice enhancers and silencers that function to bind specific proteins and promote inclusion or exclusion of exons. Alternative splice site selection is also achieved by altering the synthesis, intracellular localization, and activation of spliceosomal regulatory proteins. It has been demonstrated for several disorders that splicing can be modified using various drugs, synthetic exon-specific activators, as well as by variation in other genes. Together, these studies represent a novel approach to therapy for a wide variety of human genetic disorders. This internationally recognized panel of experts will describe elegant studies aimed at understanding the role of pre-mRNA splicing in generating protein diversity, in the development of disease, and in novel routes to therapy.
11:00 AM Oncogenic properties of alternative splicing factors. Adrian R. Krainer, Cold Spring Harbor Laboratories, NY.
11:30 AM Mechanisms of mis-regulated alternative splicing in development and disease. Tom A. Cooper, Baylor College of Medicine, Houston, TX.
12:00 NOON SCNM1, a putative RNA splicing factor that modifies disease severity in mice. Miriam Meisler, University of Michigan, Ann Arbor.
12:30 PM Spliceosome-mediated RNA trans-splicing (SMART) as an approach to gene therapy. Mariano A. Garcia-Blanco, Duke University Medical Center, Durham, NC.
