Abstract
Fluorogen-activating RNA aptamers have emerged as powerful tools for tagging and visualizing of specific RNAs in vitro and in cells. These RNA structures form specific, non-covalent complexes with conditionally fluorescent chromophores that are non-emissive while free in solution but show strongly enhanced fluorescence emission in the bound state. Another class of functional nucleic acids, called ribozymes, are enzymes made of RNA that can precisely modify their target by installing bioorthogonal functional groups or fluorescent labels. Such new functions for RNA can be evolved in the laboratory from initially random RNA libraries. In this presentation, I will highlight our work on aptamers and ribozymes and discuss recent examples of novel fluorescent nucleotide analogs.
For the RNA aptamer Chili, we engineered ligands and RNA sequences for enhanced fluorescence activation, and we gained insights into aptamer structures and fluorescence activation mechanisms [1]. We also explore the catalytic potential of DNA and RNA and use nucleic acids as catalysts for the synthesis of modified and fluorescently labeled RNA, by site-specific covalent labeling of the ribose or the nucleobase [2]. In addition, we use chemical synthesis to explore new fluorescent nucleobase analogues for responsive nucleic acid architectures [3].
References
[1] M. Mieczkowski, et al. Large Stokes shift fluorescence activation in an RNA aptamer by intermolecular proton transfer to guanine. Nat. Commun. 2021, 12, 3549. C. Steinmetzger, eta al. Structure–fluorescence activation relationships of a large Stokes shift fluorogenic RNA aptamer. Nucleic Acids Res. 2019, 47, 11538-11550.
[2] M. Ghaem Maghami, et al. Repurposing antiviral drugs for orthogonal RNA‐catalyzed labeling of RNA. Angew. Chem. Int. Ed. 2020, 59, 9335–9339.
[3] J. Dietzsch et al. Tuning exciton coupling of merocyanine nucleoside dimers by RNA, DNA and GNA double helix conformations. Angew. Chem. Int. Ed. 2022, e202116783.
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