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Interpreting the tsunami of sequence information for RNA would be facilitated by an understanding of all the physical principles determining RNA structure. In principle, a complete understanding would make it computationally possible to find RNA sequences that fold for function and to predict their three-dimensional structure. It would, thus, also facilitate discovery of new principles relating structure to function. This review covers some of the progress in understanding RNA over roughly the preceding 40 years and suggests progress still to be made., (Copyright © 2013 Wiley Periodicals, Inc.)

RNA is one class of relatively unexplored drug targets. Since RNAs play a myriad of essential roles, it is likely that new drugs can be developed that target RNA. There are several factors that make targeting RNA particularly attractive. First, the amount of information about the roles of RNA in essential biological processes is currently being expanded. Second, sequence information about targetable RNA is pouring out of genome sequencing efforts at unprecedented levels. Third, designing and screening potential oligonucleotide therapeutics to target RNA is relatively simple. The use of oligonucleotides in cell culture, however, presents several challenges such as oligonucleotide uptake and stability, and selective targeting of genes of interest. Here, we review investigations aimed at targeting RNA with oligonucleotides that can circumvent several of these potential problems. The hallmark of the strategies discussed is the use of short oligonucleotides, which may have the advantage of higher cellular uptake and improved binding selectivity compared to longer oligonucleotides. These strategies have been applied to Group I introns from the mammalian pathogens Pneumocystis carinii and Candida albicans. Both are examples of fungal infections that are increasing in number and prevalence., (Copyright 2003 Wiley Periodicals, Inc. Biopolymers 73: 151-161, 2004)

The energetics of small internal loops are important for prediction of RNA secondary and tertiary structure, selection of drug target sites, and understanding RNA structure-function relationships. Hydrogen bonding, base stacking, electrostatic interactions, backbone distortion, and base-pair size compatibility all contribute to the energetics of small internal loops. Thus, the sequence dependence of these energetics are idiosyncratic. Current approximations for predicting the free energies of internal loops consider size, asymmetry, closing base pairs, and the potential to form GA, GG, or UU pairs. The database of known three-dimensional structures allows for comparison with the models used for predicting stability from sequence., (Copyright 2001 John Wiley & Sons, Inc.)

The thermodynamics of RNA secondary structure formation in small model systems provides a database for predicting RNA structure from sequence. Methods for making these measurements are reviewed with emphasis on optical methods and treatment of experimental errors. Analysis of experimental results in terms of simple nearest-neighbor models is presented. Some measured sequence dependences of non-Watson-Crick motifs are discussed.