Evidence That microRNA Precursors, Unlike Other Non-Coding RNAs, Have Lower Folding Free Energies Than Random Sequences

Bioinformatics. 2004 Nov 22;20(17):2911-7. doi: 10.1093/bioinformatics/bth374. Epub 2004 Jun 24.


Motivation: Most non-coding RNAs are characterized by a specific secondary and tertiary structure that determines their function. Here, we investigate the folding energy of the secondary structure of non-coding RNA sequences, such as microRNA precursors, transfer RNAs and ribosomal RNAs in several eukaryotic taxa. Statistical biases are assessed by a randomization test, in which the predicted minimum free energy of folding is compared with values obtained for structures inferred from randomly shuffling the original sequences.

Results: In contrast with transfer RNAs and ribosomal RNAs, the majority of the microRNA sequences clearly exhibit a folding free energy that is considerably lower than that for shuffled sequences, indicating a high tendency in the sequence towards a stable secondary structure. A possible usage of this statistical test in the framework of the detection of genuine miRNA sequences is discussed.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics*
  • Computer Simulation
  • Drosophila melanogaster / genetics*
  • Energy Transfer
  • Humans
  • MicroRNAs / chemistry*
  • Models, Chemical*
  • Models, Statistical
  • Nucleic Acid Conformation
  • Nucleic Acid Denaturation
  • Sequence Alignment / methods*
  • Sequence Analysis, RNA / methods*
  • Structure-Activity Relationship
  • Thermodynamics


  • MicroRNAs