Poster abstracts
Poster number 55 submitted by MaKenzie Scarpitti
Biochemical dissection of translational control RBPs that are mutated in neurological disorders
MaKenzie R. Scarpitti (The Biomedical Sciences GraduateProgram, Department of Biological Chemistry and Pharmacology, Center for RNA Biology, The Ohio State University), Michael G. Kearse (The Biomedical Sciences GraduateProgram, Department of Biological Chemistry and Pharmacology, Center for RNA Biology, The Ohio State University)
Abstract:
Defects in translational control are common in many neurological disorders. In some cases, mutations in RNA-binding proteins (RBPs) that are highly enriched in the brain cause these defects and disorders. For example, loss of function of the RBP encoded by the fragile X gene, FMRP, causes fragile X syndrome (FXS) and is the leading monogenic cause of autism spectrum disorders (ASD). FMRP is thought to bind target mRNAs and then inhibit translation by sterically blocking the A site of the elongating ribosome. However, it remains highly debated how FMRP binds to mRNAs. Here, we developed a specialized reporter system using a split nanoLuciferase strategy to determine the requirements of FMRP to inhibit translation elongation. We have further adapted this approach to investigate other brain-enriched RBPs mutated in schizophrenia and ASD. Together, this work elucidates translation regulatory mechanisms that are critical to maintain homeostatic levels of protein synthesis in healthy cells and points to the mechanisms that underly neurological disease.
Keywords: translation, ribosomes, RBP