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Structure-informed design of an ultrabright RNA-activated fluorophore

Structure-informed design of an ultrabright RNA-activated fluorophore
  • Yin, P., Kuang, S. & Nie, Z. Fluorescent RNA tags for in situ RNA imaging in living cells. Anal. Sens. 3, e202200090 (2023).

    CAS 

    Google Scholar 

  • Trachman, R. J. & Ferre-D’Amare, A. R. Tracking RNA with light: selection, structure and design of fluorescence turn-on RNA aptamers. Q. Rev. Biophys. 52, e8 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Renaud de la Faverie, A., Guedin, A., Bedrat, A., Yatsunyk, L. A. & Mergny, J. L. Thioflavin T as a fluorescence light-up probe for G4 formation. Nucleic Acids Res. 42, e65 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Armitage, B. A. Imaging of RNA in live cells. Curr. Opin. Chem. Biol. 15, 806–812 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Neubacher, S. & Hennig, S. RNA structure and cellular applications of fluorescent light-up aptamers. Angew. Chem. Int. Ed. 58, 1266–1279 (2019).

    Article 
    CAS 

    Google Scholar 

  • Swetha, P., Fan, Z., Wang, F. & Jiang, J. H. Genetically encoded light-up RNA aptamers and their applications for imaging and biosensing. J. Mater. Chem. B 8, 3382–3392 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Huang, K. et al. Structure-based investigation of fluorogenic Pepper aptamer. Nat. Chem. Biol. 17, 1289–1295 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Passalacqua, L. F. M., Banco, M. T., Moon, J. D., Li, X. & Jaffrey, S. R. Ferre-D’Amare AR. Intricate 3D architecture of a DNA mimic of GFP. Nature 618, 1078–1084 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Paige, J. S., Wu, K. Y. & Jaffrey, S. R. RNA mimics of green fluorescent protein. Science 333, 642–646 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Tan, X. et al. Fluoromodules consisting of a promiscuous RNA aptamer and red or blue fluorogenic cyanine dyes: selection, characterization and bioimaging. J. Am. Chem. Soc. 139, 9001–9009 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ji, R. et al. RNA condensate as a versatile platform for improving fluorogenic RNA aptamer properties and cell imaging. J. Am. Chem. Soc. 146, 4402–4411 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Dou, C. X. et al. Genetically encoded dual-color light-up RNA sensor enabled ratiometric imaging of microRNA. Anal. Chem. 93, 2534–2540 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Bühler, B. et al. Avidity-based bright and photostable light-up aptamers for single-molecule mRNA imaging. Nat. Chem. Biol. 19, 478–487 (2023).

    Article 
    PubMed 

    Google Scholar 

  • Chen, W., Zhao, X. Y., Yang, N. Y. & Li, X. Single mRNA imaging with fluorogenic RNA aptamers and small-molecule fluorophores. Angew. Chem. Int. Ed. 62, e202209813 (2023).

    Article 
    CAS 

    Google Scholar 

  • Robinson, J. et al. Cellular visualization of G-quadruplex RNA via fluorescence- lifetime imaging microscopy. J. Am. Chem. Soc. 146, 1009–1018 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Su, Y. & Hammond, M. C. RNA-based fluorescent biosensors for live cell imaging of small molecules and RNAs. Curr. Opin. Biotechnol. 63, 157–166 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Manna, S. et al. Systematic mutation and unnatural base pair incorporation improves riboswitch-based biosensor response time. ACS Sens. 8, 4468–4472 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Dolgosheina, E. V. et al. RNA Mango aptamer-fluorophore: a bright, high-affinity complex for RNA labeling and tracking. ACS Chem. Biol. 9, 2412–2420 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Autour, A. et al. Fluorogenic RNA Mango aptamers for imaging small non-coding RNAs in mammalian cells. Nat. Commun. 9, 656 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Trachman, R. J. 3rd et al. Crystal structures of the Mango-II RNA aptamer reveal heterogeneous fluorophore binding and guide engineering of variants with improved selectivity and brightness. Biochemistry 57, 3544–3548 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Trachman, R. J. et al. Structure and functional reselection of the Mango-III fluorogenic RNA aptamer. Nat. Chem. Biol. 15, 472–479 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Trachman, R. J. III et al. Structure-guided engineering of the homodimeric Mango-IV fluorescence turn-on aptamer yields an RNA FRET pair. Structure 28, 776–785 e773 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gotrik, M. et al. Direct selection of fluorescence-enhancing RNA aptamers. J. Am. Chem. Soc. 140, 3583–3591 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ryckelynck, M. Development and applications of fluorogen/light-up RNA aptamer pairs for RNA detection and more. Methods Mol. Biol. 2166, 73–102 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Cawte, A. D., Unrau, P. J. & Rueda, D. S. Live cell imaging of single RNA molecules with fluorogenic Mango II arrays. Nat. Commun. 11, 1283 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bychenko, O. S. et al. Red light-emitting short Mango-based system enables tracking a mycobacterial small noncoding RNA in infected macrophages. Nucleic Acids Res. 51, 2586–2601 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lu, X. et al. Symmetry breaking of fluorophore binding to a G-quadruplex generates an RNA aptamer with picomolar KD. Nucleic Acids Res. 52, 8039–8051 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Falese, J. P., Donlic, A. & Hargrove, A. E. Targeting RNA with small molecules: from fundamental principles towards the clinic. Chem. Soc. Rev. 50, 2224–2243 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Childs-Disney, J. L. et al. Targeting RNA structures with small molecules. Nat. Rev. Drug Discov. 21, 736–762 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yazdani, K. et al. Machine learning informs RNA-binding chemical space. Angew. Chem. Int. Ed. 62, e202211358 (2023).

    Article 
    CAS 

    Google Scholar 

  • Warner, K. D., Hajdin, C. E. & Weeks, K. M. Principles for targeting RNA with drug-like small molecules. Nat. Rev. Drug Discov. 17, 547–558 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bancet, A. et al. Fragment linking strategies for structure-based drug design. J. Med. Chem. 63, 11420–11435 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Li, Q. Application of fragment-based drug discovery to versatile targets. Front. Mol. Biosci. 7, 180 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Koehn, J. T., Felder, S. & Weeks, K. M. Innovations in targeting RNA by fragment-based ligand discovery. Curr. Opin. Struct. Biol. 79, 102550 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Binas, O. et al. 19F NMR-based fragment screening for 14 different biologically active RNAs and 10 DNA and protein counter-screens. ChemBioChem 22, 423–433 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sreeramulu, S. et al. Exploring the druggability of conserved RNA regulatory elements in the SARS-CoV-2 genome. Angew. Chem. Int. Ed. 60, 19191–19200 (2021).

    Article 
    CAS 

    Google Scholar 

  • Cressina, E., Chen, L., Abell, C., Leeper, F. J. & Smith, A. G. Fragment screening against the thiamine pyrophosphate riboswitchthiM. Chem. Sci. 2, 157–165 (2011).

    Article 
    CAS 

    Google Scholar 

  • Zeller, M. J. et al. SHAPE-enabled fragment-based ligand discovery for RNA. Proc. Natl. Acad. Sci. USA 119, e2122660119 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Arney, W. & Weeks, K. M. RNA-ligand interactions quantified by surface plasmon resonance with reference subtraction. Biochemistry 61, 1625–1632 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Tam, B. et al. Discovery of small-molecule inhibitors targeting the ribosomal peptidyl transferase center (PTC) of M. tuberculosis. Chem. Sci. 10, 8764–8767 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Meyer, S. M. et al. DNA-encoded library screening to inform design of a Ribonuclease Targeting Chimera (RiboTAC). J. Am. Chem. Soc. 144, 21096–21102 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Connelly, C. M., Abulwerdi, F. A. & Schneekloth, J. S. Jr. Discovery of RNA binding small molecules using small molecule microarrays. Methods Mol. Biol. 1518, 157–175 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wurth, C., Grabolle, M., Pauli, J., Spieles, M. & Resch-Genger, U. Relative and absolute determination of fluorescence quantum yields of transparent samples. Nat. Protoc. 8, 1535–1550 (2013).

    Article 
    PubMed 

    Google Scholar 

  • Zhu, Y. et al. Structural modification of nonspecific thiazole orange for ligand-DNA interaction study: understanding the ligand recognition selectivity towards G4-DNA over duplex-DNA. J. Luminesc. 226, 117488 (2020).

    Article 
    CAS 

    Google Scholar 

  • Leonarski, F., D’Ascenzo, L. & Auffinger, P. Nucleobase carbonyl groups are poor Mg2+ inner-sphere binders but excellent monovalent ion binders—a critical PDB survey. RNA 25, 173–192 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Fan, Z., Dou, C. X., Tang, L. J., Wang, F. & Jiang, J. H. Genetically encoded RNA sensors for ratiometric and multiplexed imaging of small molecules in living cells. Anal. Chem. 95, 14455–14464 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Lu, X., Kong, K. Y. S. & Unrau, P. J. Harmonizing the growing fluorogenic RNA aptamer toolbox for RNA detection and imaging. Chem. Soc. Rev. 52, 4071–4098 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Chen, X. et al. Visualizing RNA dynamics in live cells with bright and stable fluorescent RNAs. Nat. Biotechnol. 37, 1287–1293 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Yang, M. et al. Targeting a noncanonical, hairpin-containing G-quadruplex structure from the MYCN gene. Nucleic Acids Res. 49, 7856–7869 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Calabrese, D. R., Connelly, C. M. & Schneekloth, J. S. Jr. Ligand-observed NMR techniques to probe RNA-small molecule interactions. Methods Enzymol. 623, 131–149 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Trachman, R. J. III, Link, K. A., Knutson, J. R. & Ferre-D’Amare, A. R. Characterizing fluorescence properties of turn-on RNA aptamers. Methods Mol. Biol. 2568, 25–36 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Winter, G. xia2: an expert system for macromolecular crystallography data reduction. J. Appl. Crystallogr. 43, 186–190 (2010).

    Article 
    CAS 

    Google Scholar 

  • Winter, G. et al. DIALS: implementation and evaluation of a new integration package. Acta Crystallogr. D Struct. Biol. 74, 85–97 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kabsch, W. Xds. Acta Crystallogr. D Biol. Crystallogr. 66, 125–132 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658–674 (2007).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126–2132 (2004).

    Article 
    PubMed 

    Google Scholar 

  • Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213–221 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Krissinel, E. & Henrick, K. Inference of macromolecular assemblies from crystalline state. J. Mol. Biol. 372, 774–797 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar 

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