RNAvigator: A Pipeline to Identify Candidates for Functional RNA Structure Elements

Abstract

Identifying structural elements in long and complex RNAs, such as long non-coding and RNA viruses, can shed light on the functionality and mechanisms of such RNAs. Here we present RNAvigator, a tool able to identify elements of structural importance by using experimental SHAPE data or SHAPE-like predictions in conjunction with stability and entropy assessments. RNAvigator recognizes regions that are the most stable, unambiguous, and structured on RNA molecules, and thus potentially functional. When relying on predictions, RNAvigator uses the CROSS algorithm, a neural network trained on experimental data that achieved an AUC of 0.74 on hepatitis C virus SHAPE-MaP data and which was able to improve the predictive power of Superfold. By using RNAvigator, we can identify known functional regions on the complete hepatitis C virus genome, including the regulatory regions CRE and IRES, and the 3’ UTR of dengue virus, a region known for the presence of structural elements essential for its replication, and functional regions of long non-coding RNAs such as XIST and HOTAIR. We envision that RNAvigator will be a useful tool for studying long and complex RNA molecules using known chemical probing data or, if they are not available, by employing predicted profiles.