Mining small RNA structure elements in untranslated regions of human and mouse mRNAs using structure-based alignment

Background: UnTranslated Regions (UTRs) of mRNAs contain regulatory elements for various aspects of mRNA metabolism, such as mRNA localization, translation, and mRNA stability. Several RNA stem-loop structures in UTRs have been experimentally identified, including the histone 3′ UTR stem-loop structure (HSL3) and iron response element (IRE). These stem-loop structures are conserved among mammalian orthologs, and exist in a group of genes encoding proteins involved in the same biological pathways. It is not known to what extent RNA structures like these exist in all mammalian UTRs. Results: In this paper we took a systematic approach, named GLEAN-UTR, to identify small stem-loop RNA structure elements in UTRs that are conserved between human and mouse orthologs and exist in multiple genes with common Gene Ontology terms. This approach resulted in 90 distinct RNA structure groups containing 748 structures, with HSL3 and IRE among the top hits based on conservation of structure. Conclusion: Our result indicates that there may exist many conserved stem-loop structures in mammalian UTRs that are involved in coordinate post-transcriptional regulation of biological pathways.