We are a basic research laboratory of Molecular Genetics that seeks to understand the influences of genetics, biochemistry and cell biology on the programmed 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 and relative abundances on codon bias-driven genetic programs involved in normal growth and in response to the physiologic states of stress and disease.
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 and programmed degradation. 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.
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