RNAelem: an algorithm for discovering sequence-structure motifs in RNA bound by RNA-binding proteins

Abstract

Motivation: RNA-binding proteins (RBPs) play a crucial role in the post-transcriptional regulation of RNA. Given their importance, analyzing the specific RNA patterns recognized by RBPs has become a significant research focus in bioinformatics. Deep Neural Networks have enhanced the accuracy of prediction for RBP-binding sites, yet understanding the structural basis of RBP-binding specificity from these models is challenging due to their limited interpretability. To address this, we developed RNAelem, which combines profile context-free grammar and the Turner energy model for RNA secondary structure to predict sequence-structure motifs in RBP-binding regions. Results: RNAelem exhibited superior detection accuracy compared to existing tools for RNA sequences with structural motifs. Upon applying RNAelem to the eCLIP database, we were not only able to reproduce many known primary sequence motifs in the absence of secondary structures, but also discovered many secondary structural motifs that contained sequence-nonspecific insertion regions. Furthermore, the high interpretability of RNAelem yielded insightful findings such as long-range base-pairing interactions in the binding region of the U2AF protein.