A collaborative project is proposed between UCSF and the Engelhardt Institute of Molecular Biology, Russian Academy of Science, Moscow, in the area of RNA conformations. The parent grant for the present proposal is GM39247 (7/1/98-6/30/02). Alternative conformations of RNA will be studied for functionally important sequences. Specifically, two cases will be investigated where conformation switching of RNA may play an important functional role: (1) structures that are formed during the dimerization of genomic RNA of avian retroviruses. (2) a hypothetical transient RNA psuedoknot at the ribosomal peptidyl transferase cancer, proposed recently by the Moscow group based on phylogenetic analysis of ribosomal RNA sequences. A set of RNA oligonucleotides (40 to 50 nucleotides in length) will be studied in solution, including sequences from a number of avian retroviruses, human and bacterial rRNA sequences, a number of mutated sequences. In this project, the Moscow group will characterize the RNA oligonucleotides by physicochemical methods and map the single- and double-stranded regions using chemicals and enzymatic probing. Based on these data, three-dimensional models will be calculated for the structures involved, and suitable sequences will be studied by UCSF groups using high resolution NMR. A reversible formation of a pseudoknot structure at certain stages of the ribosome operation may be responsible for the large-scale dynamics during protein synthesis. Understanding the detailed mechanisms of this process as well as that of the retroviral dimerization and knowledge of the structures involved may open new perspectives in designing new bacterial and antiviral therapeutic agents.