Welcome to the laboratory of Richard J. Maraia, M.D.
Section on Molecular and Cell Biology, Intramural Research Program in Genomics of Differentiation,
Eunice Kennedy Shriver National Institute of Child Health and Human Development,
National Institutes of Health, Bethesda, MD, USA
Richard J Maraia, MD
B.S., Columbia University
M.D., Cornell University Medical College
We are a basic research laboratory of Molecular Biology and Genetics that seeks to understand the influences of genetics, biochemistry and cell biology on the metabolism of small nuclear RNAs and messenger RNAs, and how these contribute to growth and development. Of molecular interest is the structural plasticity of the human La antigen and related proteins in their ability to accommodate specific binding to a variety of RNAs that differ in sequence and structure. A major interest is in the biogenesis and metabolism of transfer RNAs, the genetic adapters that translate the genetic code, and the influences of their dynamics on codon bias-driven genetic programs involved in growth and in response to physiologic stress and disease. An active project is to understand the role of the i6A37 anticodon loop modification that occurs on a small subset of tRNAs, the enzymes that mediate it, their roles in physiology and the consequences of their dysfunction.
Our group investigates the molecular mechanisms involved in RNA metabolism in eukaryotes. This includes RNA synthesis by RNA polymerase III, which serves as a model system of eukaryotic transcription, as well as the post-transcriptional phase of RNA processing, transcript maturation, degradation and decay. One focus is on the multivariate process by which a nascent tRNA precursor is converted to a mature functional tRNA. Our goal is to understand the mechanisms involved in these processes, their regulation, and how they impact upon cell growth in normal and pathological states of cellular proliferation. The La antigen and other key factors involved in pol III transcript expression are central points of focus. The mechanism of transcription termination by pol III incorporates 3' oligo-U tracts on newly synthesized transcripts, which serve as a sequence-specific binding site for the La protein. Thus, we are interested in the molecular mechanisms involved in pol III termination including oligo-U synthesis and metabolism, and its connection to posttranscriptional processing as mediated by La protein and alternative factors. Other interests include mRNA metabolism involving the human La-related protein-4 (LARP4) and its relationship to poly(A) binding protein and mRNA homeostasis. We are also interested in the expression of mobile Alu retroposons. These enigmatic genetic elements, which number nearly one million copies in human DNA, use pol III and other factors to promote their own proliferation within our genomes.