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Nucleic Acids Research, Vol 27, Issue 24 4816-4822, Copyright © 1999 by Oxford University Press

ARTICLES

No evidence that mRNAs have lower folding free energies than random sequences with the same dinucleotide distribution

C Workman and A Krogh
Center for Biological Sequence Analysis, Technical University of Denmark, Building 208, 2800 Lyngby, Denmark.

This work investigates whether mRNA has a lower estimated folding free energy than random sequences. The free energy estimates are calculated by the mfold program for prediction of RNA secondary structures. For a set of 46 mRNAs it is shown that the predicted free energy is not significantly different from random sequences with the same dinucleotide distribution. For random sequences with the same mononucleotide distribution it has previously been shown that the native mRNA sequences have a lower predicted free energy, which indicates a more stable structure than random sequences. However, dinucleotide content is important when assessing the significance of predicted free energy as the physical stability of RNA secondary structure is known to depend on dinucleotide base stacking energies. Even known RNA secondary structures, like tRNAs, can be shown to have predicted free energies indistinguishable from randomized sequences. This suggests that the predicted free energy is not always a good determinant for RNA folding.
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