Structure-based design of a sequence-specific RNA probe that mimics the kink-turn motif

Takumi Miyauchi , Kentaro Yamaguchi , Satomi Saisu , Jiro Kondo ·

YOU? · · 2025 · Open Access · · DOI: https://doi.org/10.1093/narmme/ugaf006

The technology for sequence-specific detection of RNA is in high demand in the medical field as well as in basic research in life sciences. Various methods for detecting RNA have been developed so far, but all of them are designed based solely on the rules of base complementarity, which leads to the false detection of unrelated RNAs with very similar sequences. In this study, we challenged the biomimetics approach at the molecular level to develop a sequence-specific RNA probe by mimicking a well-known RNA structural motif, the kink-turn motif, which exists in various functional RNAs. Our probe was designed in such a way that the formation of the kink-turn motif is induced only when it hybridizes with the target RNA, resulting in the exposure of the fluorescent base introduced into the probe. As we expected, both the RNA-based and DNA-based probes sensitively and selectively detected the target RNA as an increase in fluorescence intensity. We also confirmed the actuation mechanism of the probes by X-ray crystallography. This study showed that the RNA structural motifs remaining as a result of natural selection could be applied to biomimetics at the molecular level.