NIH Reporter #5R35GM118075-10

RNA-based mechanisms in nuclear steps of gene expression

Research project funded by NIGMS to study RNA-based gene expression mechanisms and their role in diseases such as neurodegeneration and retinal degeneration, using yeast as a model system.

Description

RNA-RNA and RNA-protein interactions lie at the heart of essential steps of the eukaryotic gene expression pathway. Defects in these interactions due to inherited mutations can result in age-dependent degeneration of the retina, motor neurons, and other neural tissues. The proposed studies will result in a better understanding of RNA-based mechanisms of gene expression in both the normal and disease states. In the next five years, the research will pursue three main goals using yeast Saccharomyces cerevisiae as a model system: 1. Examine the molecular mechanism of activation of the spliceosome for the first catalytic step of pre-mRNA splicing. 2. Elucidate the basis for regulation of expression of the enzyme IMPDH in purine nucleotide metabolism, related to retinitis pigmentosa. 3. Investigate the functions of hnRNP protein Hrp1 in the regulation of elongation and termination by RNA polymerase II. These studies aim to improve disease diagnosis and prognosis, and to develop new therapeutic approaches, while also illuminating basic mechanisms of eukaryotic gene expression for applications in synthetic biology and biotechnology.

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