Poster abstracts

Poster number 29 submitted by Caleb Embree

Disruption of spliceosomal proteins reduces NMD efficiency

Caleb Embree (Department of Molecular Genetics, Center for RNA Biology, Ohio State University), Andreas Stephanou (Department of Molecular Genetics, Ohio State University), Guramrit Singh (Department of Molecular Genetics, Center for RNA Biology, Ohio State University)

Regulation of the RNA lifecycle is critical to ensure proper protein production. Pre-mRNA splicing is an early RNA processing step that is tied to other downstream regulatory steps. Most notably is nonsense mediated mRNA decay (NMD), a quality control pathway that monitors translation for premature termination. Using data from the ENCODE consortium we have analyzed changes in RNA following knockdown of proteins involved in the catalytic process of splicing. Knockdown of these proteins results in the overwhelming of the NMD pathway and stabilization of NMD targets. To examine the disruption of a spliceosomal protein in a disease context we examined EFTUD2, a GTPase in the U5 snRNP. A number of pathogenic mutations in EFTUD2 reduce interactions with other members of the U5 snRNP, preventing EFTUD2's role in spliceosome activation.

Keywords: Splicing, NMD, Quality Control