STRUCTURE, MECHANISM AND CATALYSIS IN EVOLVED RIBOZYME AND RNA VIRUSES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We are investigating the structures of catalytic RNAs (or ribozymes) and RNAs derived from viruses. We have obtained new crystal structures during the last beamtime allocation period of a highly conserved region of the SARS virus RNA genome called the s2m RNA, thought to be critical to the life-cycle of this pathogenic virus, a new structure of the hammerhead ribozyme (originally discovered in the context of various plant satellite RNA viruses), and a new structure of an in vitro evolved RNA ligase that catalyzes a reaction thought to be of critical importance for the evolution of RNA selfreplication in a prebiotic RNA world. We propose to continue structural investigations of all three RNA systems during the next beamtime allocation period. Specifically, cocrystals of the SARS s2m RNA bound to peptides and small molecules, as well as SARS RNA/protein complex structures, will be solved, catalytic variants and mutants of the new hammerhead ribozyme structure will be analyzed, and a pre-ligation state of the in vitro evolved RNA ligase will be obtained.