Susan Ackerman, PhD

Professor, Departments of Neurobiology and Cellular and Molecular Medicine

HHMI Investigator

UC San Diego 

Host(s): Kapil Ramachandran (Faculty)

Transfer RNAs as Modifiers of Neurological Phenotypes

Growing evidence indicates that neurons are particularly reliant on the spatial and temporal regulation of mRNA translation for their survival and function; and mutations in numerous components of the translational machinery have been linked to neurological disorders. Using a forward genetic approach in mice, we identified a point mutation in a neuron-specific, nuclear tRNA gene which exacerbates neurodegeneration in mice homozygous for mutations in ribosome rescue factors. In addition, we have found that this tRNA mutation modifies seizure threshold and alters neuronal excitability. These modifications are accompanied by widespread transcriptional reprogramming and changes in translational signaling pathways. Recently we have shown that expression of these RNA Pol III-regulated genes is controlled in a tissue-specific manner, suggesting that mutations in these genes will have cell-specific impacts. Work is ongoing to understand the basis of the regulation of these genes. Together, our work highlights the exquisite sensitivity of the nervous system to subtle changes in mRNA translation homeostasis and raises the possibility that the regulation of tRNA expression may play a critical role in complex neuronal processes and phenotypic modification of genetic disorders.

Relevant Publications: 

Ribosome stalling induced by mutation of a CNS-specific tRNA causes neurodegeneration 

Expression of the Neuronal tRNA n-Tr20 Regulates Synaptic Transmission and Seizure Susceptibility

Tuesdays@10 is a signature Zuckerman Institute initiative that aims to expose researchers at all levels to high-quality science and stimulate scientific discourse. The speakers featured in this series represent various fields and techniques in neuroscience, and include invited guests of the Columbia Neuroscience Seminars, the Zuckerman Institute's Local Circuits Affiliates Program, and other special seminar series through a combined, collaborative effort of one or more of the following: Columbia's Zuckerman Institute, the Center for Precision Psychiatry, the Center for Theoretical Neuroscience, the Department of Neuroscience, the Doctoral Program in Neurobiology and Behavior and the Columbia Translational Neuroscience Initiative, and with support from the Kavli Institute for Brain Science. 

More information and a full schedule can be found here.