Nicholas J. Reiter, Ph.D.
Assistant Professor of Biochemistry
670 Robinson Research Building
Nashville, TN 37232-0146
The focus of our research is to understand the fundamental properties of ribonucleic acid (RNA) and how it interacts with protein molecules that are involved in cancer. RNA is unique because it is the only biological molecule that can both carry genetic information and perform chemical reactions by acting as an enzyme. A key property of RNA that allows it to perform a diversity of biological tasks is its ability to fold into a wide range of complex, three-dimensional structures. The focus of our research involves elucidating these RNA three-dimensional structures and determining if specific RNA molecules and RNA-protein interactions play a direct role in cancer pathways. We use a combination of discovery biochemistry and structural biology to learn more about the role of RNA in human disease processes.
- BA, Carleton College, Northfield MN
- PhD, University of Wisconsin-Madison
Thousands of functional RNA molecules exist in the human genome and do not encode protein sequences. We are just now beginning to understand how the diversity, structural complexity, and plasticity of regulatory RNAs help to drive evolution, development, and cellular differentiation. Indeed, it is the union of these non-coding RNAs with the capacity and efficiency of protein molecules that collectively serves to orchestrate and expand the complexity of an organism.
Our research group applies macromolecular crystallography and NMR techniques to understand how RNA and protein (ribonucleoprotein (RNP)) complexes regulate gene expression. Protein-RNA recognition events are central to biology and misregulation of these interactions leads to human disease and oncogenesis. A key to understanding RNP biological function is having knowledge of how they assemble and are structured three-dimensionally.
There are two main areas of interest in the lab. i) RNA processing that occurs in human mitochondria. For example, a variety of diseases such as neuromuscular and neurodegenerative disorders have been linked to specific mutations within mitochondrial tRNAs (mt-tRNAs). It appears that human mt-tRNAs contain very low sequence conservation compared to the classically defined tRNA elements, and that many mt-tRNAs are structurally unique molecules. How do RNA processing enzymes, such as RNase P, accommodate this structural diversity? And how do specific point mutations in human mt-tRNA lead to disease? A second area of interest includes ii) investigating non-protein coding RNAs (ncRNAs) and RNP complexes that serve to regulate transcription and gene expression in mammals. A new paradigm has been established showing that several large, structured ncRNAs can mediate transcriptional repression by directly interacting with chromatin or chromatin remodeling enzymes. We aim to combine traditional and emerging structural biology methods to better understand how some of these large ncRNAs are structured at the atomic level and how they function as part of an RNP complex to regulate gene expression.