Poster abstracts

Poster number 112 submitted by Carrie Rollins

Structural insights into the recognition of HIV acceptor splice sites by the UP1 domain of hnRNP A1

Carrie Rollins (Department of Chemistry, Case Western Reserve ), Dr. Jeffrey Levengood (Department of Chemistry, Case Western Reserve), Dr. Blanton Tolbert (Department of Chemistry, Case Western Reserve)

Abstract:
Alternative splicing of the human immunodeficiency virus (HIV) genome is a carefully orchestrated event with a strong impact on both function and infectivity. This splicing is accomplished by the cis RNA regulatory elements interacting with trans host regulatory proteins. One such cis regulatory element is the third stem loop of acceptor splice site A7, termed exon splicing silencer 3 or SL^ESS3. Utilization of this splice site in combination with donor splice site D4 produces tat and rev mRNA. Although SL^ESS3 has been shown to interact with the UP1 domain of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) to block the assembly of the spliceosome, the mechanism of binding has yet to be determined. Biophysical studies have been implemented to further the understanding of this interaction, through mutational analysis, isothermal titration calorimetry, and two dimensional NMR. These studies provide insight into the elements of both SL^ESS3 and UP1 that contribute to the formation of this RNA-protein complex.

Keywords: Alternative Splicing, NMR