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Large-scale analysis of small molecule-RNA interactions using multiplexed RNA structure libraries

BiochemistryLarge-scale analysis of small molecule-RNA interactions using multiplexed RNA structure libraries


  • 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 

  • Sztuba-Solinska, J., Chavez-Calvillo, G. & Cline, S. E. Unveiling the druggable RNA targets and small molecule therapeutics. Bioorg. Med. Chem. 27, 2149–2165 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Guan, L. & Disney, M. D. Recent advances in developing small molecules targeting RNA. ACS Chem. Biol. 7, 73–86 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Bush, J. A. et al. Systematically studying the effect of small molecules interacting with RNA in cellular and preclinical models. ACS Chem. Biol. 16, 1111–1127 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hargrove, A. E. Small molecule–RNA targeting: starting with the fundamentals. Chem. Commun. 56, 14744–14756 (2020).

    Article 
    CAS 

    Google Scholar 

  • Cheung, A. K. et al. Discovery of small molecule splicing modulators of survival motor neuron-2 (SMN2) for the treatment of spinal muscular atrophy (SMA). J. Med. Chem. 61, 11021–11036 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sturm, S. et al. A phase 1 healthy male volunteer single escalating dose study of the pharmacokinetics and pharmacodynamics of risdiplam (RG7916, RO7034067), a SMN2 splicing modifier. Br. J. Clin. Pharmacol. 85, 181–193 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Bose, D. et al. The tuberculosis drug streptomycin as a potential cancer therapeutic: inhibition of miR-21 function by directly targeting its precursor. Angew. Chem. Int. Ed. 51, 1019–1023 (2012).

    Article 
    CAS 

    Google Scholar 

  • Vo, D. D. et al. Targeting the production of oncogenic microRNAs with multimodal synthetic small molecules. ACS Chem. Biol. 9, 711–721 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Velagapudi, S. P., Gallo, S. M. & Disney, M. D. Sequence-based design of bioactive small molecules that target precursor microRNAs. Nat. Chem. Biol. 10, 291–297 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Velagapudi, S. P. et al. Design of a small molecule against an oncogenic noncoding RNA. Proc. Natl Acad. Sci. USA. 113, 5898–5903 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Liu, X. et al. Targeted degradation of the oncogenic microRNA 17-92 cluster by structure-targeting ligands. J. Am. Chem. Soc. 142, 6970–6982 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yan, H., Bhattarai, U., Guo, Z.-F. & Liang, F.-S. Regulating miRNA-21 biogenesis by bifunctional small molecules. J. Am. Chem. Soc. 139, 4987–4990 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wong, C.-H. et al. Targeting toxic RNAs that cause myotonic dystrophy type 1 (DM1) with a bisamidinium inhibitor. J. Am. Chem. Soc. 136, 6355–6361 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Rzuczek, S. G. et al. Precise small-molecule recognition of a toxic CUG RNA repeat expansion. Nat. Chem. Biol. 13, 188–193 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Reddy, K. et al. A CTG repeat-selective chemical screen identifies microtubule inhibitors as selective modulators of toxic CUG RNA levels. Proc. Natl Acad. Sci. USA. 116, 20991–21000 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lee, J. et al. Intrinsically cell-penetrating multivalent and multitargeting ligands for myotonic dystrophy type 1. Proc. Natl Acad. Sci. USA. 116, 8709–8714 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Shibata, T. et al. Small molecule targeting r(UGGAA)n disrupts RNA foci and alleviates disease phenotype in Drosophila model. Nat. Commun. 12, 236 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Howe, J. A. et al. Selective small-molecule inhibition of an RNA structural element. Nature 526, 672–677 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Fedorova, O. et al. Small molecules that target group II introns are potent antifungal agents. Nat. Chem. Biol. 14, 1073–1078 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Rangan, R. et al. De novo 3D models of SARS-CoV-2 RNA elements from consensus experimental secondary structures. Nucleic Acids Res. 49, 3092–3108 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Velagapudi, S. P. et al. Defining RNA–small molecule affinity landscapes enables design of a small molecule inhibitor of an oncogenic noncoding RNA. ACS Central Sci. 3, 205–216 (2017).

    Article 
    CAS 

    Google Scholar 

  • Ursu, A. et al. Gini coefficients as a single value metric to define chemical probe selectivity. ACS Chem. Biol. 15, 2031–2040 (2020).

  • Mukherjee, H. et al. PEARL-seq: a photoaffinity platform for the analysis of small molecule–RNA interactions. ACS Chem. Biol. 15, 2374–2381 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Disney, M. D. Targeting RNA with small molecules to capture opportunities at the intersection of chemistry, biology, and medicine. J. Am. Chem. Soc. 141, 6776–6790 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Endoh, T., Ohyama, T. & Sugimoto, N. RNA-capturing microsphere particles (R-CAMPs) for optimization of functional aptamers. Small 15, 1805062 (2019).

    Article 

    Google Scholar 

  • Satpathi, S., Endoh, T., PodbevÅ¡ek, P., Plavec, J. & Sugimoto, N. Transcriptome screening followed by integrated physicochemical and structural analyses for investigating RNA-mediated berberine activity. Nucleic Acids Res. 49, 8449–8461 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kwok, C. K., Marsico, G., Sahakyan, A. B., Chambers, V. S. & Balasubramanian, S. rG4-seq reveals widespread formation of G-quadruplex structures in the human transcriptome. Nat. Methods 13, 841–844 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Murat, P., Guilbaud, G. & Sale, J. E. DNA polymerase stalling at structured DNA constrains the expansion of short tandem repeats. Genome Biol. 21, 209 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Komatsu, K. R. et al. RNA structure-wide discovery of functional interactions with multiplexed RNA motif library. Nat. Commun. 11, 6275 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lin, K.-Y. & Matteucci, M. D. A cytosine analogue capable of clamp-like binding to a guanine in helical nucleic acids. J. Am. Chem. Soc. 120, 8531–8532 (1998).

    Article 
    CAS 

    Google Scholar 

  • Murase, H. & Nagatsugi, F. Development of the binding molecules for the RNA higher-order structures based on the guanine-recognition by the G-clamp. Bioorg. Med. Chem. Lett. 29, 1320–1324 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Murase, H., Nagatsugi, F. & Sasaki, S. Development of a selective ligand for G–G mismatches of CGG repeat RNA inducing the RNA structural conversion from the G-quadruplex into a hairpin-like structure. Org. Biomol. Chem. 20, 3375–3381 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Krishnamurthy, M., Schirle, N. T. & Beal, P. A. Screening helix-threading peptides for RNA binding using a thiazole orange displacement assay. Biorg. Med. Chem. 16, 8914–8921 (2008).

    Article 
    CAS 

    Google Scholar 

  • Asare-Okai, P. N. & Chow, C. S. A modified fluorescent intercalator displacement assay for RNA ligand discovery. Anal. Biochem. 408, 269–276 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Tran, T. & Disney, M. D. Identifying the preferred RNA motifs and chemotypes that interact by probing millions of combinations. Nat. Commun. 3, 1125 (2012).

    Article 
    PubMed 

    Google Scholar 

  • Sato, Y. et al. Trimethine cyanine dyes as deep-red fluorescent indicators with high selectivity to the internal loop of the bacterial A-site RNA. Chem. Commun. 55, 3183–3186 (2019).

    Article 
    CAS 

    Google Scholar 

  • Sato, Y. et al. Strong binding and off–on signaling functions of deep-red fluorescent TO-PRO-3 for influenza A virus RNA promoter region. ChemBioChem 20, 2752–2756 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zhang, J., Umemoto, S. & Nakatani, K. Fluorescent indicator displacement assay for ligand−RNA interactions. J. Am. Chem. Soc. 132, 3660–3661 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Murata, A., Harada, Y., Fukuzumi, T. & Nakatani, K. Fluorescent indicator displacement assay of ligands targeting 10 microRNA precursors. Biorg. Med. Chem. 21, 7101–7106 (2013).

    Article 
    CAS 

    Google Scholar 

  • Fukuzumi, T., Murata, A., Aikawa, H., Harada, Y. & Nakatani, K. Exploratory study on the RNA-binding structural motifs by library screening targeting pre-miRNA-29a. Chem. Eur. J. 21, 16859–16867 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Wicks, S. L. & Hargrove, A. E. Fluorescent indicator displacement assays to identify and characterize small molecule interactions with RNA. Methods 167, 3–14 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • del Villar-Guerra, R., Gray, R. D., Trent, J. O. & Chaires, J. B. A rapid fluorescent indicator displacement assay and principal component/cluster data analysis for determination of ligand–nucleic acid structural selectivity. Nucleic Acids Res. 46, e41 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Das, B., Murata, A. & Nakatani, K. A small-molecule fluorescence probe ANP77 for sensing RNA internal loop of C, U and A/CC motifs and their binding molecules. Nucleic Acids Res. 49, 8462–8470 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Shibata, T. et al. Fluorescent indicator displacement assay for the discovery of UGGAA repeat-targeted small molecules. Chem. Commun. 59, 5071–5074 (2023).

    Article 
    CAS 

    Google Scholar 

  • Largy, E., Hamon, F. & Teulade-Fichou, M.-P. Development of a high-throughput G4-FID assay for screening and evaluation of small molecules binding quadruplex nucleic acid structures. Anal. Bioanal. Chem. 400, 3419–3427 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Agard, N. J., Prescher, J. A. & Bertozzi, C. R. A strain-promoted [3 + 2] azide−alkyne cycloaddition for covalent modification of biomolecules in living systems. J. Am. Chem. Soc. 126, 15046–15047 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Debets, M. F., van der Doelen, C. W., Rutjes, F. P. & van Delft, F. L. Azide: a unique dipole for metal-free bioorthogonal ligations. ChemBioChem 11, 1168–1184 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Lorenz, R. et al. ViennaRNA Package 2.0. Algorithms Mol. Biol. 6, 26 (2011).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Popenda, M. et al. Automated 3D structure composition for large RNAs. Nucleic Acids Res. 40, e112 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Biesiada, M., Pachulska-Wieczorek, K., Adamiak, R. W. & Purzycka, K. J. RNAComposer and RNA 3D structure prediction for nanotechnology. Methods 103, 120–127 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Mukohyama, J. et al. miR-221 targets QKI to enhance the tumorigenic capacity of human colorectal cancer stem cells. Cancer Res. 79, 5151–5158 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Elyakim, E. et al. hsa-miR-191 is a candidate oncogene target for hepatocellular carcinoma therapy. Cancer Res. 70, 8077–8087 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Si, M. L. et al. miR-21-mediated tumor growth. Oncogene 26, 2799–2803 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Bai, L.-P., Hagihara, M., Nakatani, K. & Jiang, Z.-H. Recognition of chelerythrine to human telomeric DNA and RNA G-quadruplexes. Sci. Rep. 4, 6767 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Basu, P. & Suresh Kumar, G. Small molecule–RNA recognition: binding of the benzophenanthridine alkaloids sanguinarine and chelerythrine to single stranded polyribonucleotides. J. Photochem. Photobiol. B: Biology 174, 173–181 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Chen, H. et al. Chelerythrine as a fluorescent light-up ligand for an i-motif DNA structure. New J. Chem. 45, 28–31 (2021).

    Article 

    Google Scholar 

  • Mondal, S., Jana, J., Sengupta, P., Jana, S. & Chatterjee, S. Myricetin arrests human telomeric G-quadruplex structure: a new mechanistic approach as an anticancer agent. Mol. Biosyst. 12, 2506–2518 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Das, A., Majumder, D. & Saha, C. Correlation of binding efficacies of DNA to flavonoids and their induced cellular damage. J. Photochem. Photobiol. B: Biology 170, 256–262 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Khan, E. et al. Myricetin reduces toxic level of CAG repeats RNA in Huntington’s disease (HD) and spino cerebellar ataxia (SCAs). ACS Chem. Biol. 13, 180–188 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Gaillard, P. et al. Design and synthesis of the first generation of novel potent, selective, and in vivo active (benzothiazol-2-yl)acetonitrile Inhibitors of the c-Jun N-terminal kinase. J. Med. Chem. 48, 4596–4607 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sato, Y., Saito, H., Aoki, D., Teramae, N. & Nishizawa, S. Lysine linkage in abasic site-binding ligand–thiazole orange conjugates for improved binding affinity to orphan nucleobases in DNA/RNA hybrids. Chem. Commun. 52, 14446–14449 (2016).

    Article 
    CAS 

    Google Scholar 

  • Pei, R., Rothman, J., Xie, Y. & Stojanovic, M. N. Light-up properties of complexes between thiazole orange-small molecule conjugates and aptamers. Nucleic Acids Res. 37, e59 (2009).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Simon, L. M. et al. In vivo analysis of influenza A mRNA secondary structures identifies critical regulatory motifs. Nucleic Acids Res. 47, 7003–7017 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Manfredonia, I. et al. Genome-wide mapping of SARS-CoV-2 RNA structures identifies therapeutically-relevant elements. Nucleic Acids Res. 48, 12436–12452 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Rangan, R. et al. RNA genome conservation and secondary structure in SARS-CoV-2 and SARS-related viruses: a first look. RNA 26, 937–959 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ikeda, S., Kubota, T., Yuki, M. & Okamoto, A. Exciton-controlled hybridization-sensitive fluorescent probes: multicolor detection of nucleic acids. Angew. Chem. Int. Ed. 48, 6480–6484 (2009).

    Article 
    CAS 

    Google Scholar 

  • Ikeda, S. et al. Hybridization-sensitive fluorescence control in the near-infrared wavelength range. Org. Biomol. Chem. 9, 4199–4204 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Stootman, F. H., Fisher, D. M., Rodger, A. & Aldrich-Wright, J. R. Improved curve fitting procedures to determine equilibrium binding constants. Analyst 131, 1145–1151 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Kerpedjiev, P., Hammer, S. & Hofacker, I. L. Forna (force-directed RNA): simple and effective online RNA secondary structure diagrams. Bioinformatics 31, 3377–3379 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Dominguez, D. et al. Sequence, structure, and context preferences of human RNA binding proteins. Mol. Cell 70, 854–867.e859 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

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