The Yang laboratory investigates the structures and functions of various viral and bacterial RNA-protein complexes involved in RNA synthesis using cryo-electron microscopy (cryo-EM) and complementary biochemical, cell biological and computational approaches. A particular emphasis in the lab's research is placed on unravelling the molecular mechanism of coronavirus (SARS-CoV-2, SARS-CoV and MERS-CoV) genome replication and transcription.
Coronaviruses are positive-strand RNA viruses with genomes approximately 30 kb in length, which is substantially larger than the average-sized RNA virus genome. To maintain the genome integrity and viral fitness, the coronavirus genome encodes a unique proofreading 3ʹ–5ʹ exoribonuclease to improve the fidelity of RNA synthesis. RNA synthesis requires specific recognition of structured RNA elements, many of which located in the 5ʹ and 3ʹ untranslated regions (UTRs) of the viral genome, by various viral nonstructural proteins (nsps) and host factors. Our current research focuses on the following three aspects of coronavirus RNA synthesis: i) to delineate the interactions between viral proteins and 3ʹ UTR/5ʹ UTR during replication and transcription initiation, ii) to elucidate the structural basis of proofreading during coronavirus RNA synthesis, and iii) to determine the RNA-RNA and RNA-protein interactions mediating template switch, a complex process that occurs during the synthesis of (–)RNA intermediates and is essential for the expression of coronavirus structural and accessory proteins.