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MING WU

RNA Folding

The secondary structure of the p5abc subdomain (a 56-nucleotide RNA) of the tetrahymena thermophyla group I intron has been determined by NMR. Its secondary structure in aqueous solution is significantly different from the subdomain in a crystal as part of the P4-P6 domain. It is also different from the secondary structure obtained by phylogenetic analysis of group I introns, but it is consistent with thermodynamic predictions. In the presence of magnesium, p5abc subdomain folds into a tertiary structure with a secondary structure consistent with the crystal secondary structure, but completely different from the one in the absence of magnesium. Magnesium-mediated RNA tertiary folding causes significant secondary structure rearrangement. The common assumption that RNA folds by first forming secondary structure, then forming tertiary interactions from unpaired bases, is not always correct.

The three-dimensional structure deterrnination of p5abc in absence of magnesium is being analyzed. It should be solved in the near future, and can serve as a model for functional analysis. Collaboration with Prof. Thomas Cechís group to test this new folding mechanism on the P4-P6 domain (a 160-nucleotide RNA) has started.

 
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