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The long-term goal of our research is to understand nature’s strategies to diversify the structures and functions of RNA through chemical modifications and base pairing patterns; in so doing, we want to develop new methods for synthesizing modified RNA molecules as molecular tools for biomedical applications.

The past three decades have witnessed the great era of nucleic acids research with the discovery of new functions of RNAs as catalysts and regulators of numerous biochemical reactions in addition to the carriers of genetic information, the adapters in protein synthesis and the structural scaffolds in subcellular organelles. On the other hand, however, comparing to proteins that contain more than 20 different amino acid residues, RNA only contain four types of nucleobases. In order to achieve the structural and functional diversity, nature uses over 150 chemical modifications to decorate RNAs in all the three primary domains of life. Many of these modifications have been demonstrated to play critical roles in a variety of human diseases and biological processes such as embryonic stem cell differentiation, development, regulation of RNA stability, circadian rhythms, temperature adaptation, meiotic progression, and regulation of RNA-RNA and RNA-protein binding interactions. More interestingly, it is believed that these chemical modifications are the most evolutionarily conserved properties in RNAs, and some of the modified nucleobases are relics of the RNA World, where they may have enhanced the chemical diversity of RNA prior to protein. In addition to chemical modifications, both DNA and RNA can further diversify their structures and functions by different folding patterns into well-defined duplex, hairpin, cruciform, triplex and quadruplex etc., which are mainly stabilized by both canonical Watson-Crick pairs and non-canonical Wobble, Hoogsteen, and metal-mediated base pairs, as well as other tertiary interactions. Therefore, studying natural chemical modifications and base-base interactions in DNA/RNA is important for the further elucidation of their biological functions, the development of new therapeutics, and the exploration in the origins of life.

We are also interested in developing novel RNA based catalysts for organic reactions and studying their catalytic mechanisms. Hybrid catalysis, which combines the high efficiency of active transition metals and the high chirality of biopolymer scaffolds (protein, DNA and RNA), represents a new generation of catalytic strategy. These scaffolds can transfer their chirality and promote a transformation with good enantioselectivity. Based on the ‘RNA World Hypothesis’ and the beautiful homochirality of life, most likely it’s RNA that originated the chiral transformation in the early stage of life. Comparing to DNA and protein, RNA can fold into more diversified structures that can dynamically bind and activate the substrates, meaning that RNA can play more roles than merely the chiral scaffolds. By optimizing both RNA and metal ligands, we are trying to develop some high efficient catalysts for general organic reactions. 

To achieve these goals, we use multidisciplinary research approaches and techniques in organic synthesis, biophysics, biochemistry, cell biology and structure biology.

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