Clusters of mammalian conserved RNA structures in UTRs associate with RBP binding sites

RNA secondary str uct ures play essential roles in the formation of the tertiary str uct ure and function of a transcript. Recent genome-wide studies highlight significant potential for RNA str uct ures in the mammalian genome. Ho w e v er, a major challenge is assigning functional roles to these str uct ured RNAs. In this study, we conduct a guilt-b y -association analy sis of clusters of computationally predicted conserved RNA str uct ure (CRSs) in human untranslated regions (UTRs) to associate them with gene functions. We filtered a broad pool of ∼50 0 0 0 0 human CRSs for UTR o v erlap, resulting in 4734 and 24 754 CRSs from the 5 ' and 3 ' UTR of protein-coding genes, respectively. We separately clustered these CR Ss f or both sets using RNAscClust, obtaining 793 and 2403 clusters, each containing an a v erage of fiv e CR Ss per cluster. We identified o v errepresented binding sites for 60 and 43 RNA-binding proteins co-localizing with the clustered CRSs. Furthermore, 104 and 441 clusters from the 5 _ and 3 _ UTRs, respectiv ely, sho w ed enrichment for various Gene Ontologies, including biological processes such as 'signal transduction', 'nerv ous sy stem de v elopment', molecular functions lik e 'transferase activity' and the cellular components such as 'synapse' among others. Our study shows that significant functional insights can be gained by clustering RNA str uct ures based on their str uct ural characteristics.