The secondary structure of an RNA must be known before the relationship between its structure and function can be determined. One way to predict the secondary structure of an RNA is to identify covarying residues that maintain the pairings (Watson-Crick, Wobble and non-canonical pairings). This comparative approach consists of identifying mutations from homologous sequence alignments. The sequences must covary enough for compensatory mutations to be revealed, but comparison is difficult if they are too different. Thus the choice of homologous sequences is critical. While many possible combinations of homologous sequences may be used for prediction, only a few will give good structure predictions. This can be due to poor quality alignment in stems or to the variability of certain sequences. This problem of sequence selection is currently unsolved.