Thursday, March 28 2019
Room 1005, Roger A. and Helen B. Krone Engineered Biosystems Building (EBB), 950 Atlantic Dr NW, Atlanta, GA 30332
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Assembly of Macromolecular RNA-Protein Machines: Insights into Regulation of snoRNP Biogenesis

Homa Ghalei, Ph.D.
Department of Biochemistry
Emory University School of Medicine

Non-coding (nc)RNAs account for the majority of the transcriptional output. Yet, their precise function and mode of regulation remain largely unclear. The interaction of ncRNAs with proteins for the formation of ribonucleoproteins (RNPs) dictates the spatial and temporal action of many of the cellular machines and is critically important for the regulation of gene expression. The complex assembly of small nucleolar (sno)RNPs for methylation and processing of the ribosomal RNA is an example of such regulated biogenesis and is essential in all eukaryotes from yeast to man. Although the major interacting partners of snoRNAs have been well-known for some time, the regulatory mechanisms that control the biogenesis and turnover of these important RNAs, which likely underlie their link to cancer, are not understood. This constitutes a critical gap in our current understanding of the function of snoRNAs and their involvement in diseases, which we aim to fill. Yeast genetics allows us to identify key interaction partners and essential steps in biogenesis and turnover of snoRNPs. Biochemical assays and enzyme kinetics enable us to in vitro reconstitute and validate our in vivo findings. Structural techniques allow us to uncover the molecular mechanism of the assembly of snoRNAs with their key protein partners. Together, our projects combine a multifaceted approach to provide a molecular understanding of how snoRNPs are regulated in the cell. Characterizing these regulatory mechanisms will reveal novel paradigms of RNA control in the cell that may be also used for controlling the level of other disease-related cellular ncRNAs.

Host: Francesca Storici, Ph.D.