Identification of potentially new bifunctional RNA based on genome-wide data-mining of alternative splicing events.

It is now evident that the transcriptional output of the genome is much more complex than estimates based on the number of protein-coding genes, and that non-coding RNA widely increase the source of regulatory molecules, a role previously ascribed to proteins. Furthermore, the recent characterization of bifunctional RNA, i.e. RNA for which both coding capacity and activity as functional RNA have been reported, adds an additional degree of complexity. Based on the SRA (Steroid Receptor RNA Activator) model, where bifunctionality is regulated by alternative splicing, we hypothesized that similar cases, not yet formally tested experimentally, might exist. Using freely available data from high-throughput sequencing projects, we propose here a bioinformatical identification of mRNA whose ORF are disrupted by alternative splicing events, especially by intron retention, and potentially representing a cognate non-coding RNA. Our data-mining approach revealed that the human genome contains around 300 possibilities of potentially new bifunctional RNA.