Translational fidelity and neurodegeneration - Susan Ackerman

Stanford Neurosciences Institute Seminar Series Presents

Translational fidelity and neurodegeneration

Susan Ackerman, Ph.D

Stephen W. Kuffler Chair in Biology, Professor Cellular and Molecular Medicine

Host: Gregor Bieri

Abstract

The faithful execution of protein production from mRNAs is largely controlled by accurate charging of tRNAs by the aminoacyl tRNA tRNA synthetases. Many of these enzymes have editing domains that can recognize and correct mischarging of cognate tRNAs. We previously identified a spontaneous mutation in the editing domain of the mouse alanyl tRNA-synthetase gene which leads to aggregates of misfolded proteins and degeneration of cerebellar Purkinje cells. By forward genetics we have identified a modifier gene of this mutation that prevents aggregate formation and neurodegeneration. Our data demonstrates that this novel vertebrate-specific protein plays an important, previously unappreciated role in translational fidelity.