N6 -Isopentenyladenosine in RNA Determines the Cleavage Site of Endonuclease Deoxyribozymes.

Angewandte Chemie
Anam LiaqatClaudia Höbartner

Abstract

RNA-cleaving deoxyribozymes can serve as selective sensors and catalysts to examine the modification state of RNA. However, site-specific endonuclease deoxyribozymes that selectively cleave post-transcriptionally modified RNA are extremely rare and their specificity over unmodified RNA is low. We report that the native tRNA modification N6 -isopentenyladenosine (i6 A) strongly enhances the specificity and has the power to reconfigure the active site of an RNA-cleaving deoxyribozyme. Using in vitro selection, we identified a DNA enzyme that cleaves i6 A-modified RNA at least 2500-fold faster than unmodified RNA. Another deoxyribozyme shows unique and unprecedented behaviour by shifting its cleavage site in the presence of the i6 A RNA modification. Together with deoxyribozymes that are strongly inhibited by i6 A, these results highlight that post-transcriptional RNA modifications modulate the catalytic activity of DNA in various intricate ways.

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Citations

Sep 19, 2020·Chemical Society Reviews·Ronald Micura, Claudia Höbartner
Jun 30, 2021·Angewandte Chemie·Anam LiaqatClaudia Höbartner

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