Shrisha Bollu
Pronouns: She/her
Research Mentor(s): Anthony Antonellis
Research Mentor School/College/Department: Human Genetics and Neurology / Medicine
Program: UROPF
Session: Session 1 (9:00am – 9:50am)
Authors: Shrisha Bollu, Sheila Marte, Anthony Antonellis
Abstract
Aminoacyl tRNA synthetases (ARS) are enzymes involved in protein translation. ARSs are essential and ubiquitously-expressed proteins responsible for attaching amino acids to its corresponding tRNA molecules. However, mutations in six genes encoding an ARS result in a dominantly-inherited neurodegenerative condition known as peripheral neuropathy. Peripheral neuropathies affect the peripheral nervous system, where patients display a loss of motor and sensory function in their distal extremities. In collaboration with neurologists, we identified three asparaginyl tRNA synthetase (NARS1) variants in patients with peripheral neuropathy. All three NARS1 variants segregate with disease, occur at highly-conserved positions between evolutionary-diverse species, and are not found in the general population, all of which builds strong evidence for pathogenicity. However, the functional consequences of these mutations on NARS1 is unknown. To investigate this question, we developed a humanized yeast assay to test the effects of the mutated human NARS1 gene on yeast growth. We expect the NARS1 variants to be associated with reduced yeast growth compared to wild-type NARS1, consistent with a loss-of-function effect as seen in other neuropathy-associated ARS variants. In conclusion, we expect NARS1 mutations to exhibit a loss-of-function effect, which then provides evidence toward a pathogenic mechanism of NARS1-mediated neuropathy.
