Alu elements are retrotransposons that comprise roughly 11% of the human genome. Alu elements can be transcribed independently (AluRNA) as part of their retrotransposition pathway or embedded within other RNA species. Alu 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 Alu elements, robust and comprehensive structural information is limited. A canonical structure for AluRNA is defined, but it does not capture the impact of sequence context for Alu sequences embedded within other RNA species. Here, we characterize the RNA secondary structures of six unique mRNA 3′ UTR-embedded Alu elements using dimethyl sulfate probing coupled with mutational profiling (DMS-MaP), measured in cells. Our findings suggest that mRNA-embedded Alu elements do not systematically conform to the self-contained canonical AluRNA secondary structure; instead, each Alu element appears to adopt a unique structure. These structural data expand the known RNA structure space assumed by Alu elements and suggest that diversity in RNA structures underlies the diverse biological functions attributed to Alu elements.
Abigail Lehr (Sat,) studied this question.