The Diverse RNA Structures of Alu Elements

<em>Alu</em> elements are retrotransposons that comprise roughly 11% of the human genome. <em>Alu</em> elements can be transcribed independently (<em>Alu</em>RNA) as part of their retrotransposition pathway or embedded within other RNA species. <em>Alu</em> elements inserted into mRNAs assume diverse roles in both normal biology and in disease states. These elements can contain alternative polyadenylation signals, influence transcription and translation efficiency, modulate splicing, and serve as favorable sites for ADAR editing. Despite the known diversity in the sequence and function of mRNA-embedded <em>Alu</em> elements, robust and comprehensive structural information is limited. A canonical structure for <em>Alu</em>RNA is defined, but it does not capture the impact of sequence context for <em>Alu</em> sequences embedded within other RNA species. Here, we characterize the RNA secondary structures of six unique mRNA 3&prime; UTR-embedded <em>Alu</em> elements using dimethyl sulfate probing coupled with mutational profiling (DMS-MaP), measured in cells. Our findings suggest that mRNA-embedded <em>Alu</em> elements do not systematically conform to the self-contained canonical <em>Alu</em>RNA secondary structure; instead, each <em>Alu</em> element appears to adopt a unique structure. These structural data expand the known RNA structure space assumed by <em>Alu</em> elements and suggest that diversity in RNA structures underlies the diverse biological functions attributed to <em>Alu</em> elements.