Elucidating the RNA Structure of Alu Elements (2024)

Undergraduate: Abigail Lehr

Faculty Advisor: Kevin Weeks
Department: Biology, Chemistry

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Alu elements are a family of largely inactive retrotransposons that comprise around 11% of the human genome, mostly encoded in intronic sequences. Over evolutionary time, Alu elements have evolved into three families, J, S, and Y. Moreover, there is substantial evidence that suggests a role of Alu elements in both normal biology and disease states. Their abundance and disease relevance characterize Alu elements as an enticing therapeutic target. However, a lack of robust structural information exists beyond a widely reported, single, general structure, despite the known diversity in sequence and function. To elucidate the secondary structures of previously uncharacterized Alu elements, we utilize an in vitro approach involving chemical probing coupled with mutational profiling. Our findings from this experimentation suggest that intronic Alu elements do not systematically conform to the expected secondary structure; instead, each appears to adopt a unique structure. Furthermore, Alu elements appear to interact with their biological flanking sequences, countering the accepted notion that the RNA structure of Alu elements is self-contained. By exploring the RNA structure space assumed by Alu elements and generating robust, chemical probing-informed structural data, we can open the doors to novel therapeutic targets.