Poster abstracts

Poster number 93 submitted by Stephanie Nguyen

Analysis of alternative splicing in disease associated exons

Stephanie Nguyen (Biology, Lewis University), Jessica King (Biology, Lewis University)

Abstract:
The process of pre-mRNA splicing involves the removal of introns, the noncoding regions within an RNA transcript, and the ligation of coding regions, or exons. Alternative splicing maintains gene regulation through a variation in the specific patterns of exon inclusion and intron exclusion in the final mRNA transcript. This also allows for individual genes to code for multiple proteins, which contributes to diversity. Approximately 33% of genetic mutations are thought to be the result of an improper regulation in splicing causing a disease. It is known that RNA structure can have an influence on alternative splicing patterns. Additionally, the RNA binding protein, Drosha, generally identifies and excises RNA hairpins, but it was recently shown to also act as a splicing factor in a cleavage-independent manner. Therefore, it is thought that Drosha can alter the inclusion rates of exons that form hairpins or the inclusion of exons near a hairpin structure. Drosha expression is known to be altered in some cancers and therefore there may be changes in alternative splicing in disease states. HeLa and HEK-293T cell lines were used in order to determine the alternative splicing patterns of hairpin-structured exons, or those near known miRNAs in cancerous and non-cancerous cells. The spliced ratios were compared to identify genes in which splicing may become altered in disease states where Drosha expression is also altered. The role of Drosha in alternative splicing of these structured exons will be investigated.

References:
Kahn, D.H., Jahan, S., Davie, J.R. (2012) Pre-mRNA splicing: Role of epigenetics and implications in disease. Advances in Biological Regulation. 52:3, 377-388.

Lim KH, Ferraris L, Filloux ME, Raphael BJ, Fairbrother WG. Using positional distribution to identify splicing elements and predict pre-mRNA processing defects in human genes. Proceedings of the National Academy of Sciences of the United States of America. 2011;108:11093–11098.

McManus CJ, Graveley BR. RNA structure and the mechanisms of alternative splicing. Curr Opin Genet Dev. 2011 Aug;21(4):373-9.

Keywords: Alternative Splicing , Drosha