National Institute of Neurological Disorders and Stroke 1F31NS147773-01

Functional and biochemical analysis of RNA exosome variants linked to neurological disorders

The award funds research to study mutations in the RNA exosome linked to neurological and cardiac disorders by modeling these mutations in yeast to understand their functional and structural impacts.

Description

This project aims to analyze a series of missense mutations in the EXOSC5 subunit of the RNA exosome to understand how these mutations alter RNA exosome function and lead to disease. The study will model these mutations in budding yeast (Saccharomyces cerevisiae) due to the evolutionary conservation of the RNA exosome. Five mutations (rrp46-Q86I, rrp46-L127T, rrp46-L191H, rrp46-C202L, rrp46-V73K) associated with neurodevelopmental and cardiac pathologies will be examined. Objectives include examining the impact of each mutation on RNA exosome function through functional assays and transcriptomics, and assessing the structural integrity and interactions of the RNA exosome with each mutation via co-migration assays and suppressor screens.

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