Key result
Local-minimisation of free energy with thermodynamic fluctuations during RNA synthesis can result in different predicted secondary structures compared to global-minimum free energy approaches.
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Progressive folding models of RNA secondary structure may provide different and potentially more biologically relevant predictions than global-minimum free energy models.
Secondary structures within the 5' untranslated regions of messenger RNAs can have profound effects on the efficiency of translation of their messages and thereby on gene expression. Consequently they can act as important regulatory motifs in both physiological and pathological settings. Current approaches to predicting the secondary structure of these RNA sequences find the structure with the global-minimum free energy. However, since RNA folds progressively from the 5' end when synthesised or released from the translational machinery, this may not be the most probable structure. We discuss secondary structure prediction based on local-minimisation of free energy with thermodynamic fluctuations as nucleotides are added to the 3' end and show that these can result in different secondary structures. We also discuss approaches for studying the extent of the translational inhibition specified by structures within the 5' untranslated region.
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Hughes et al. (2006) studied RNA secondary structure and gene expression. Local-minimisation of free energy with thermodynamic fluctuations vs. Global-minimum free energy was evaluated. Local-minimisation of free energy with thermodynamic fluctuations during RNA synthesis can result in different predicted secondary structures compared to global-minimum free energy approaches.
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