An improved secondary structure computation method and its application to intervening sequences in the human alpha-like globin mRNA precursors
Laboratory of Mathematical Biology, Division of Cancer Biology and Diagnosis, National Cancer Institute, National Institutes of Health Frederick, MD 21701, USA
1Shanghai Institute of Biochemistry, Chinese Academy of Sciences Shanghai 200031, China
2Advanced Scientific Computer Laboratory Program Resources, Inc. NCI/FCRF, Frederick, MD 21701, USA
3Sackler Institute for Molecular Medicine Sacker Faculty of Medicine, Tel Aviv University Ramat Aviv, Israel
Current secondary structure prediction computations have a serious drawback. The calculated thermodynamically most stable structure often differs from that observed in solution or in crystal form. In this paper we suggest a way to partially overcome some of these limitations by simulating the RNA folding process and calculating the frequencies of occurrence of the various substructures obtained. The frequently recurring substructures are then selected to construct the secondary structure of the whole RNA. 142 tRNA molecules and an E. coli 16S rRNA molecule have been examined by this method. The percentages of successful prediction of the correct helices are significantly higher than those calculated previously. 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 composed of the statistically more significant substructures. This has also been demonstrated by using randomly shuffled sequences. The secondary structures of each of the randomized sequences are computed and their mean and standard deviations are used in evaluating the significance of the substructures obtained in the folding of the biological sequence. Some potentially appealing structural features aligning adjacent exons for ligation have been found.
Received on April 3, 1987; accepted on October 18, 1987