High-throughput functional profiling and evolutionary covariation analysis of entire riboswitch sequences

L. M. Hertz, A. Arce, E. Rivas, J. B. Lucks. (2025). doi: 10.1101/2025.11.18.689055
Links: BioRxiv

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We developed a method to identify full riboswitch sequences starting from their conserved aptamer domains, extending them to include expression platforms, and then using computational and high-throughput functional assays to filter and characterize them. Applying this approach to fluoride, ZTP, lysine, and TPP riboswitches, we generated complete sequence covariation models that reveal structural rearrangements and provide new insights into riboswitch mechanism and RNA dynamics.

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