Comparison of MRNA secondary-structure folding properties across whole transcriptomes, 2005

Several studies have demonstrated that mRNA stability may be an important factor in gene expression. mRNA-protein interactions are known to regulate gene expression including pre-mRNA splicing, polyadenylation, editing, transport, cytoplasmic targeting, translation, and mRNA turnover. We explored well-defined mRNAs of less than 3000 base pairs in size, to determine the effects the major dinucleotide distribution has on the folding free energy. A comparative study was conducted preserving dinucleotide composition (Dishuffled), compared to changing the dinucleotide composition (Monoshuffled). Statistical analysis (ANOVA) between the native mRNA and its randomized sequences, and comparing all mRNAs in the human transcriptome, found that the native mRNAs were more stable (greater negative free energy of folding). We examined if clustering of genes associated with the three Gene Ontology GO Consortium categories molecular function, biological process, and cellular components. We linked the folding free energies of mRNA secondary structure to their GO terms. Out of 18, 969 GO terms, we found 5 terms were the Z-score was -1.69 or less resulting in 95% or higher confidence interval. Apoptotic associated GO terms have the largest accumulative frequency of the most negative Z-scores. The human transcriptome was compared to mouse and arabidopsis. The native mRNAs in these transcriptomes were more negative than the Monoshuffled gene set; which suggests that evolution has selected codons that favor the potential for formation of mRNA structures that contribute to global folding stability