The workhorse of protein synthesis is the ribosome. Ribosomes are large macromolecular assemblies consisting of RNA (specifically ribosomal RNA) and a variety of unique proteins. We are  interested in understanding the process of ribosome maturation. From birth to their final maturation, ribosomal RNAs in animal and plant cells are trimmed, chemically modified, and possibly folded by a class of novel enzymes, called small nucleolar ribonucleoprotein particles (snoRNPs). Unlike commonly known enzymes that are composed of either protein or RNA, snoRNPs contain both protein and RNA. While the RNA component is responsible for specific interaction with the target RNA, the protein components are responsible for the actual catalytic reactions. Thus, snoRNPs possess the characteristics of both kinds of biomolecules and have greater potential to catalyze chemical reactions for a diverse range of substrates. From a chemical point of view, the fascinating aspects of this enzyme are its structural layout and how this structure entails its catalytic power. 

Box C/D snoRNPs are responsible for site specific 2’-O-methylation of nearly 100 rRNAs. A subclass of the box C/D snoRNPs processes precursor rRNA by specifically cleave precursor rRNA. Box C/D snoRNPs are comprised of at least four proteins (Nop56, Nop58, fibrillarin, Snu13/15.5 kD/L7Ae) and a guide RNA (box C/D RNA). Structures of the archaeal homologs of the box C/D snoRNP proteins are being determined in our laboratory. We are interested in understanding how these proteins interact among each other and with the guide and target RNA molecules.

Box H/ACA snoRNPs are responsible for site-specific isomerization of more than 100 uridines in ribosomal and small nuclear RNAs. Vertebrate telomerase RNA contains a box H/ACA RNA domain that assembles with the core proteins. The H/ACA domain, although not guiding pseudouridylation, is responsible for the biogenesis of telomerase RNA. We are interested in understanding how this class of snoRNPs function in ribosome and telomerase biogenesis.

          A Model of C/D sRNP assembly                                                              A Model of H/ACA sRNP assembly