An improved secondary structure computation method and its application to intervening sequences in the human alpha-like globin mRNA precursors

Current secondary structure prediction computations have a seriousdrawback. The calculated thermodynamically most stable structureoften differs from that observed in solution or in crystal form.In this paper we suggest a way to partially overcome some ofthese limitations by simulating the RNA folding process andcalculating the frequencies of occurrence of the various substructuresobtained. The frequently recurring substructures are then selectedto construct the secondary structure of the whole RNA. 142 tRNAmolecules and an E. coli 16S rRNA molecule have been examinedby this method. The percentages of successful prediction ofthe correct helices are significantly higher than those calculatedpreviously. The secondary structures of intervening sequences(IVSs) excised from human -like globin pre-mRNAs are also computed.Thus, in this method the secondary structures obtained are composedof the statistically more significant substructures. This hasalso been demonstrated by using randomly shuffled sequences.The secondary structures of each of the randomized sequencesare computed and their mean and standard deviations are usedin evaluating the significance of the substructures obtainedin the folding of the biological sequence. Some potentiallyappealing structural features aligning adjacent exons for ligationhave been found. Received on April 3, 1987; accepted on October 18, 1987