Folding and finding RNA secondary structure.
Optimal exploitation of the expanding database of sequences requires rapid finding and folding of RNAs. Methods are reviewed that automate folding and discovery of RNAs with algorithms that couple thermodynamics with chemical mapping, NMR, and/or sequence comparison. New functional noncoding RNAs in genome sequences can be found by combining sequence comparison with the assumption that functional noncoding RNAs will have more favorable folding free energies than other RNAs. When a new RNA is discovered, experiments and sequence comparison can restrict folding space so that secondary structure can be rapidly determined with the help of predicted free energies. In turn, secondary structure restricts folding in three dimensions, which allows modeling of three-dimensional structure. An example from a domain of a retrotransposon is described. Discovery of new RNAs and their structures will provide insights into evolution, biology, and design of therapeutics. Applications to studies of evolution are also reviewed.
Mathews
David H
DH
Department of Biochemistry and Biophysics and Center for RNA Biology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
Moss
Walter N
WN
Turner
Douglas H
DH
D019295:Computational Biology / Q000379:methods*; D030541:Databases, Genetic; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D022661:RNA, Untranslated / Q000737:chemistry*; D018626:Retroelements / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software; D013816:Thermodynamics
D022661:RNA, Untranslated; D018626:Retroelements