A deep learning model for characterizing protein-RNA interactions from sequences at single-base resolution

Protein-RNA interactions play pivotal roles in regulating transcription, translation, and RNA metabolism. Characterizing these interactions offers key insights into RNA dysregulation mechanisms. Here, we introduce Reformer, a deep learning model that predicts protein-RNA binding affinity from sequence data. Trained on 225 enhanced cross-linking and immunoprecipitation sequencing (eCLIP-seq) datasets encompassing 155 RNA-binding proteins across three cell lines, Reformer achieves high accuracy in predicting binding affinity at single-base resolution. The model uncovers binding motifs that are often undetectable through traditional eCLIP-seq methods. Notably, the motifs learned by Reformer are shown to correlate with RNA processing functions. Validation via electrophoretic mobility shift assays confirms the model's precision in quantifying the impact of mutations on RNA regulation. In summary, Reformer improves the resolution of RNA-protein interaction predictions and aids in prioritizing mutations that influence RNA regulation.