ShapeRNA: an integrated web server for RNA secondary structure, ensemble, and functional analysis

RNA secondary structure plays a critical role in gene regulation, yet existing computational and experimental tools for structure analysis are often fragmented across prediction, ensemble modeling, and functional interpretation workflows. Here, we present ShapeRNA, a user-friendly web server for integrated RNA secondary structure prediction, ensemble inference, and structure-aware regulatory annotation. ShapeRNA supports three complementary analytical workflows, including sequence-based structure prediction, reactivity-guided modeling using SHAPE or DMS data, and sequencing-guided ensemble inference from high-throughput probing experiments. The platform integrates multiple established prediction algorithms and provides standardized data processing, ensemble clustering, and visualization. In addition, ShapeRNA enables mapping of RNA modification sites, microRNA target regions, and RNA-binding protein interaction motifs onto predicted RNA structures and representative ensemble conformations. We demonstrate the utility of ShapeRNA through applications including analysis of mutation-associated structural changes in MAPT exon 10, characterization of conformational heterogeneity in the HIV-1 Rev Response Element, and regulatory annotation of the oncogenic long non-coding RNA HULC. ShapeRNA provides an accessible and extensible platform for investigating RNA structural heterogeneity and regulatory mechanisms. This website is free and open to all users, and there is no login requirement. The server is accessible at https://shaperna.com.