The ensemble diversity of non-coding RNA structure is lower than random sequence

In addition to energetically optimal structures, RNAs can fold into near energy suboptimal conformations that may be populated and play functional roles. The diversity of this structural ensemble can be estimated using a metric derived from the calculated RNA partition function: the ensemble diversity. In this report, 10 classes of functional RNAs were analyzed: the 5.8S and 5S rRNAs, ribozyme, RNase P, snoRNA, snRNA, SRP RNA, tmRNA, Vault RNA and Y RNA. Representative sequences from each class were mutagenized in two ways: firstly, all possible point mutations were generated and secondly, wild type sequences were randomized to generate multiple scrambled mutants. Compared to the mutants, the native RNA ensemble diversity was predicted to be lower. This finding held true when all available sequences (378,455 sequences) for each RNA class (archived in the RNAcentral database) were analyzed. This suggests that a compact structural ensemble is an evolved characteristic of functional RNAs.