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

This work investigates whether mRNA has a lower estimated folding free ener gy than random sequences. The free energy estimates are calculated by the m fold program for prediction of RNA secondary structures. For a set of 46 mR NAs it is shown that the predicted free energy is not significantly differe nt from random sequences with the same dinucleotide distribution. For rando m sequences with the same mononucleotide distribution it has previously bee n shown that the native mRNA sequences have a lower predicted free energy, which indicates a more stable structure than random sequences. However, din ucleotide 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 indist inguishable from randomized sequences. This suggests that the predicted fre e energy is not always a good determinant for RNA folding.