Federal Grant Award Summary

The National Institute of Environmental Health Sciences (NIEHS) awarded UC Riverside a $120,663 Project Grant (CFDA 93.113: Environmental Health program) effective April 1, 2026, through March 31, 2028, to conduct mechanistic research on how environmental exposures alter RNA pseudouridylation and subsequent RNA-protein interactions in the context of amyotrophic lateral sclerosis (ALS) pathogenesis. The research deliverables include three specific research aims: (1) examining how RNA pseudouridylation is modulated by xenobiotic exposure in human neuronal cells; (2) investigating transcriptome-wide occupancy impacts of ALS-associated proteins influenced by RNA pseudouridylation; and (3) exploring the functional impacts of RNA pseudouridylation and pseudouridine-protein interactions in xenobiotic and ALS pathological contexts. This investigation is designed to bridge existing knowledge gaps regarding the mechanistic link between environmental exposure and ALS through the lens of RNA modification and protein-RNA binding dynamics.

The project builds upon preliminary data demonstrating that ALS-linked mutations in profilin-1 reduce its affinity for pseudouridine-containing RNA, suggesting that environmental exposure-mediated aberrant RNA pseudouridylation constitutes a major regulatory mechanism underlying neurodegenerative disease pathogenesis. The research outputs will advance understanding of how environmental xenobiotic exposure alters fundamental RNA processes and protein interactions relevant to ALS development and may inform future intervention strategies for environmental health-related neurological disease.