Affiliations

Director, Biochemistry, Biophysics & Structural Biology GPB Home Area

Associate Professor, Biological Chemistry

Member, Gene Regulation GPB Home Area, JCCC Gene Regulation Program Area

My research group is interested to understand how non-coding RNAs function by forming defined three-dimensional structures and by interacting with proteins. In particular, we are investigating how a class of small RNAs (called microRNA or miRNA) is processed in human. The projects will be investigated using X-ray crystallography, biochemistry and in vitro evolution methods. MiRNAs are involved in many important biological functions, and are emerged as a new class of oncogenes and tumor suppressors. They regulate the expression of many protein-coding genes by targeting their messenger RNAs (mRNAs) for degradation or translational repression. To become the short mature functional forms, the long primary transcripts (pri-miRNAs) need to be specifically recognized and cleaved by a series of cellular processing factors. The first step of this processing pathway involves two protein factors, Drosha (a ribonuclease III family member) and DGCR8 (an RNA binding protein). We are characterizing the RNA binding and cleavage properties of these proteins, in the hope to use the knowledge to improve the algorithms to predict new miRNA genes and to design gene knockdown technologies by mimicking pri-miRNA. We recently found surprisingly that DGCR8 is a heme-binding protein and heme is likely involved in the regulation of miRNA processing. Our findings have important implications to the biological functions of miRNAs and heme, and to the pathogenesis and therapies of diseases such as cancers and Alzheimer's disease.