Research in the Li Laboratory
1. Assembly of ribonucleoprotein particles (RNPs)
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.
2. CRISPR – a small RNA-based immunity pathway
Nearly 40% bacterial and all archaeal genomes contain Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) loci that are recently shown to offer the organisms a small RNA-based immunity system against invading foreign nucleic acids. The CRISPR loci contain DNA fragments from the invading nucleic acids integrated into the regularly spaced repeat sequences that are then used to recognize the nucleic acids from subsequent infections. The CRISPR and associated proteins (Cas proteins) function by degrading the invading nucleic acids using short RNAs from the CRISPR transcripts as guides and protein as nucleases. We are interested in the molecular processes of the CRISPR-Cas mediated immunity.
Undergraduate Research Opportunity: Dr. Hong Li’s laboratory accepts highly dedicated and motivated students who are interested in biochemistry and biophysics research of biomolecules. Research topics range from aging, cancer, biotechnology development, to three-dimensional structure computation. The research experience can prepare individuals for pursuing advanced degrees in related fields and jobs in biotech industry and government labs. We are especially interested in accepting freshman and sophomore students who understand the value of research.