Structure and Function of Non-coding RNAs and RNPs
Our Passion is to Understand How RNA Structure Promotes the Chemistry of Life
Although many human diseases are caused by mis-splicing of genes, we still do not fully understand the fundamental mechanisms that drive the function of the splicing machinery or how non-coding RNAs propagate and spread within our genome.
Group II introns are mobile genetic elements that are the likely evolutionary ancestors of both the spliceosome and active human retrotransposons. Thus, these ribozymes offer a simplified system to study these fundamental cellular processes. These primitive ribozymes often contain an intron-encoded protein (IEP) that assists splicing to form ribonucleoprotein (RNP) complexes, which act as selfish retroelements that copy and integrate into new genomic locations. In humans, retroelement mobility cause disease by disrupting open reading frames, altering gene regulation, and triggering genomic rearrangements. Long term, we aim to harness the highly sequence specific properties of these movements for biotechnology and gene therapy applications.
The overall goal of our lab is to determine the detailed molecular mechanisms of how intron RNPs form and how these RNPs spread introns to new locations in DNA by combining biochemical and structural biology approaches. Our lab is currently using multiple structural biology methods to understand the structure of the intron ribozyme and the RNP complex, including X-ray crystallography, cryo-electron microscopy (cryo-EM), and small angle X-ray scattering (SAXS). Structural studies are aided and complemented through biochemical, molecular, and bacterial genetic approaches.
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