Strategies for targeting RNA with small molecule drugs

References

• Goh K-I, Cusick ME, Valle D, et al. The human disease network. Proc Nat Acad Sci. 2007;104(21):8685–8690.
   PubMed Web of Science ®Google Scholar
• Makley LN, Gestwicki JE. Expanding the number of ‘druggable’ targets: non-enzymes and protein–protein interactions. Chem Biol Drug Des. 2013;81(1):22–32.
   PubMed Web of Science ®Google Scholar
• Djebali S, Davis CA, Merkel A, et al. Landscape of transcription in human cells. Nature. 2012 October 01;489(7414):101–108.
   PubMed Web of Science ®Google Scholar
• Westhof E, Fritsch V. RNA folding: beyond Watson–Crick pairs. Structure. 2000 March 01;8(3):R55–R65.
   PubMed Web of Science ®Google Scholar
• Weeks KM, Crothers DM. Major groove accessibility of RNA. Science. 1993 Sep 17;261(5128):1574–1577.
   PubMed Web of Science ®Google Scholar
• Moore PB. Structural Motifs in RNA. Annu Rev Biochem. 1999 June 01;68(1):287–300.
   PubMedGoogle Scholar
• Leontis NB, Lescoute A, Westhof E. The building blocks and motifs of RNA architecture. Curr Opin Struct Biol. 2006;16(3):279–287.
   PubMed Web of Science ®Google Scholar
• Gardner PP, Giegerich R. A comprehensive comparison of comparative RNA structure prediction approaches. BMC Bioinf. 2004;5(1):140.
   PubMedGoogle Scholar
• Lorenz R, Bernhart SH, Höner Zu Siederdissen C, et al. ViennaRNA package 2.0. Algorithms Mol Biol. 2011 November 24;6(1):26.
   PubMed Web of Science ®Google Scholar
• Zuker M, Stiegler P. Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information. Nucleic Acids Res. 1981 Jan 10;9(1):133–148.
   PubMed Web of Science ®Google Scholar
• Freier SM, Kierzek R, Jaeger JA, et al. Improved free-energy parameters for predictions of RNA duplex stability. Proc Natl Acad Sci USA. 1986;83(24):9373–9377.
   PubMed Web of Science ®Google Scholar
• Mathews DH, Sabina J, Zuker M, et al. Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure11Edited by I. Tinoco. J Mol Biol. 1999 May 21;288(5):911–940.
   PubMed Web of Science ®Google Scholar
• Zhao Q, Zhao Z, Fan X, et al. Review of machine learning methods for RNA secondary structure prediction. Plos Comput Biol. 2021;17(8):e1009291.
   PubMed Web of Science ®Google Scholar
• Dowell RD, Eddy SR. Evaluation of several lightweight stochastic context-free grammars for RNA secondary structure prediction. BMC Bioinf. 2004 Jun 4;5(1):71.
   PubMedGoogle Scholar
• Do CB, Woods DA, Batzoglou S. CONTRAfold: RNA secondary structure prediction without physics-based models. Bioinformatics. 2006;22(14):e90–e98.
   PubMed Web of Science ®Google Scholar
• Singh J, Hanson J, Paliwal K, et al. RNA secondary structure prediction using an ensemble of two-dimensional deep neural networks and transfer learning. Nat Commun. 2019 November 27;10(1):5407.
   PubMedGoogle Scholar
• Sato K, Akiyama M, Sakakibara Y. RNA secondary structure prediction using deep learning with thermodynamic integration.Nat Commun. 2021 February 11;12(1):941.
   PubMed Web of Science ®Google Scholar
• Weeks KM. Advances in RNA structure analysis by chemical probing. Curr Opin Struct Biol. 2010;20(3):295–304.
   PubMed Web of Science ®Google Scholar
• RajBhandary UL, Chang SH, Sneider J. Studies on polynucleotides. LXXXII. Yeast phenylalanine transfer ribonucleic acid: partial digestion with ribonuclease T-1 and derivation of the total primary structure. J Biol Chem. 1968 Feb 10;243(3):598–608.
   PubMed Web of Science ®Google Scholar
• Ehresmann C, Baudin F, Mougel M, et al. Probing the structure of RNAs in solution. Nucleic Acids Res. 1987 Nov 25;15(22):9109–9128.
   PubMed Web of Science ®Google Scholar
• Peattie DA, Gilbert W. Chemical probes for higher-order structure in RNA. Proc Natl Acad Sci U S A. 1980;77(8):4679–4682.
   PubMed Web of Science ®Google Scholar
• Inoue T, Cech TR. Secondary structure of the circular form of the Tetrahymena rRNA intervening sequence: a technique for RNA structure analysis using chemical probes and reverse transcriptase. Proc Natl Acad Sci U S A. 1985;82(3):648–652.
   PubMed Web of Science ®Google Scholar
• Rouskin S, Zubradt M, Washietl S, et al. Genome-wide probing of RNA structure reveals active unfolding of mRNA structures in vivo. Nature. 2014;505(7485):701–705.
   PubMed Web of Science ®Google Scholar
• Zubradt M, Gupta P, Persad S, et al. DMS-MaPseq for genome-wide or targeted RNA structure probing in vivo. Nat Methods. 2017 January 01;14(1):75–82.
   PubMed Web of Science ®Google Scholar
• Low JT, Weeks KM. SHAPE-directed RNA secondary structure prediction. Methods. 2010 October 01;52(2):150–158.
   PubMed Web of Science ®Google Scholar
• Smola MJ, Weeks KM. In-cell RNA structure probing with SHAPE-MaP.Nat Protoc. 2018 June 01;13(6):1181–1195.
   PubMed Web of Science ®Google Scholar
• Hajdin Christine E, Bellaousov S, Huggins W, et al. Accurate SHAPE-directed RNA secondary structure modeling, including pseudoknots. Proc Nat Acad Sci. 2013 April 02;110(14):5498–5503.
   PubMed Web of Science ®Google Scholar
• Reyes FE, Garst AD, Batey RT. Strategies in RNA crystallography. Methods Enzymol. 2009;469:119–139.
   PubMed Web of Science ®Google Scholar
• Barnwal RP, Yang F, Varani G. Applications of NMR to structure determination of RNAs large and small. Arch Biochem Biophys. 2017;628:42–56.
   PubMed Web of Science ®Google Scholar
• Townshend Raphael JL, Eismann S, Watkins Andrew M, et al. Geometric deep learning of RNA structure. Science. 2021 August 27;373(6558):1047–1051.
   PubMed Web of Science ®Google Scholar
• Schatz A, Bugle E, Waksman SA. Streptomycin, a substance exhibiting antibiotic activity against gram-positive and gram-negative bacteria.Pro Soc Exp Biol Med. 1944 January 01;55(1):66–69.
   Google Scholar
• Luzzatto L, Apirion D, Schlessinger D. Mechanism of action of streptomycin in E. coli: interruption of the ribosome cycle at the initiation of protein synthesis.Proc Nat Acad Sci. 1968 July 01;60(3):873–880.
   PubMed Web of Science ®Google Scholar
• Fourmy D, Recht MI, Blanchard SC, et al. Structure of the A site of Escherichia coli 16S ribosomal RNA complexed with an aminoglycoside antibiotic. Science. 1996 Nov 22;274(5291):1367–1371.
   PubMed Web of Science ®Google Scholar
• Maiti M, Nauwelaerts K, Herdewijn P. Pre-microRNA binding aminoglycosides and antitumor drugs as inhibitors of Dicer catalyzed microRNA processing. Bioorg Med Chem Lett. 2012 Feb 15;22(4):1709–1711.
   PubMed Web of Science ®Google Scholar
• Ennifar E, Paillart J-C, Bodlenner A, et al. Targeting the dimerization initiation site of HIV-1 RNA with aminoglycosides: from crystal to cell. Nucleic Acids Res. 2006;34(8):2328–2339.
   PubMed Web of Science ®Google Scholar
• Wilson DN, Schluenzen F, Harms JM, et al. The oxazolidinone antibiotics perturb the ribosomal peptidyl-transferase center and effect tRNA positioning. Proc Nat Acad Sci. 2008;105(36):13339–13344.
   PubMed Web of Science ®Google Scholar
• Pandit N, Singla RK, Shrivastava B. Current updates on oxazolidinone and its significance. Int J Med Chem. 2012 February 26;2012:159285.
   PubMedGoogle Scholar
• Means J, Katz S, Nayek A, et al. Structure-activity studies of oxazolidinone analogs as RNA-binding agents. Bioorg Med Chem Lett. 2006 Jul 1;16(13):3600–3604.
   PubMed Web of Science ®Google Scholar
• Mandal M, Breaker RR. Gene regulation by riboswitches.Nat Rev Mol Cell Biol. 2004 June 01;5(6):451–463.
   PubMed Web of Science ®Google Scholar
• Mironov AS, Gusarov I, Rafikov R, et al. Sensing small molecules by nascent RNA: a mechanism to control transcription in bacteria. Cell. 2002 Nov 27;111(5):747–756.
   PubMed Web of Science ®Google Scholar
• Winkler W, Nahvi A, Breaker RR. Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression. Nature. 2002 Oct 31;419(6910):952–956.
   PubMed Web of Science ®Google Scholar
• Wachter A, Tunc-Ozdemir M, Grove BC, et al. Riboswitch control of gene expression in plants by splicing and alternative 3’ end processing of mRNAs. Plant Cell. 2007 Nov;19(11):3437–3450.
   PubMed Web of Science ®Google Scholar
• Croft MT, Moulin M, Webb ME, et al. Thiamine biosynthesis in algae is regulated by riboswitches. Proc Nat Acad Sci. 2007;104(52):20770–20775.
   PubMed Web of Science ®Google Scholar
• Kubodera T, Watanabe M, Yoshiuchi K, et al. Thiamine-regulated gene expression of Aspergillus oryzae thiA requires splicing of the intron containing a riboswitch-like domain in the 5’-UTR. FEBS Lett. 2003 Dec 18;555(3):516–520.
   PubMed Web of Science ®Google Scholar
• Blount KF, Breaker RR. Riboswitches as antibacterial drug targets. Nat Biotechnol. 2006 Dec;24(12):1558–1564.
   PubMed Web of Science ®Google Scholar
• Sudarsan N, Cohen-Chalamish S, Nakamura S, et al. Thiamine pyrophosphate riboswitches are targets for the antimicrobial compound pyrithiamine. Chem Biol. 2005 Dec;12(12):1325–1335.
   PubMedGoogle Scholar
• Lee ER, Blount KF, Breaker RR. Roseoflavin is a natural antibacterial compound that binds to FMN riboswitches and regulates gene expression. RNA Biol. 2009 Apr-Jun;6(2):187–194.
   PubMed Web of Science ®Google Scholar
• Consortium EP. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489(7414):57–74.
   PubMed Web of Science ®Google Scholar
• Gebert LFR, MacRae IJ. Regulation of microRNA function in animals.Nat Rev Mol Cell Biol. 2019 January 01;20(1):21–37.
   PubMed Web of Science ®Google Scholar
• Gumireddy K, Young DD, Xiong X, et al., Small-molecule inhibitors of microRNA miR-21 function. Angew Chem Int Ed Engl. 2008;47(39):7482–7484.
   PubMed Web of Science ®Google Scholar
• Velagapudi Sai P, Cameron Michael D, Haga Christopher L, et al. Design of a small molecule against an oncogenic noncoding RNA. Proc Nat Acad Sci. 2016 May 24;113(21):5898–5903.
   PubMed Web of Science ®Google Scholar
• Costales MG, Haga CL, Velagapudi SP, et al. Small molecule inhibition of microRNA-210 reprograms an oncogenic hypoxic circuit. J Am Chem Soc. 2017 March 08;139(9):3446–3455.
   PubMed Web of Science ®Google Scholar
• Haga CL, Velagapudi SP, Strivelli JR, et al. Small molecule inhibition of miR-544 biogenesis disrupts adaptive responses to hypoxia by modulating ATM-mTOR signaling. ACS Chem Biol. 2015 Oct 16;10(10):2267–2276.
   PubMed Web of Science ®Google Scholar
• Young DD, Connelly CM, Grohmann C, et al. Small molecule modifiers of microRNA miR-122 function for the treatment of hepatitis C virus infection and hepatocellular carcinoma. J Am Chem Soc. 2010 Jun 16;132(23):7976–7981.
   PubMed Web of Science ®Google Scholar
• Todd PK, Paulson HL. RNA-mediated neurodegeneration in repeat expansion disorders. Ann Neurol. 2010;67(3):291–300.
   PubMed Web of Science ®Google Scholar
• Turner C, Hilton-Jones D. The myotonic dystrophies: diagnosis and management. J Neurol Neurosurg. 2010;81(4):358.
   PubMed Web of Science ®Google Scholar
• Zu T, Cleary JD, Liu Y, et al. RAN translation regulated by muscleblind proteins in myotonic dystrophy type 2. Neuron. 2017;95(6):1292–1305.e5.
   PubMed Web of Science ®Google Scholar
• Wheeler TM, Sobczak K, Lueck JD, et al. Reversal of RNA dominance by displacement of protein sequestered on triplet repeat RNA. Science (New York, NY). 2009;325(5938):336–339.
   Google Scholar
• Warf MB, Nakamori M, Matthys CM, et al. Pentamidine reverses the splicing defects associated with myotonic dystrophy. Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18551–18556.
   PubMed Web of Science ®Google Scholar
• Childs-Disney JL, Stepniak-Konieczna E, Tran T, et al. Induction and reversal of myotonic dystrophy type 1 pre-mRNA splicing defects by small molecules. Nat Commun. 2013 June 28;4(1):2044.
   PubMedGoogle Scholar
• Angelbello Alicia J, Rzuczek Suzanne G, McKee KK, et al. Precise small-molecule cleavage of an r(CUG) repeat expansion in a myotonic dystrophy mouse model. Proc Nat Acad Sci. 2019 April 16;116(16):7799–7804.
   PubMed Web of Science ®Google Scholar
• Nguyen L, Luu LM, Peng S, et al. Rationally designed small molecules that target both the DNA and RNA causing myotonic dystrophy type 1. J Am Chem Soc. 2015 November 11;137(44):14180–14189.
   PubMed Web of Science ®Google Scholar
• Lee Y, Rio DC. Mechanisms and regulation of alternative Pre-mRNA splicing. Annu Rev Biochem. 2015;84(1):291–323.
   PubMedGoogle Scholar
• Blumenfeld A, Slaugenhaupt SA, Axelrod FB, et al. Localization of the gene for familial dysautonomia on chromosome 9 and definition of DNA markers for genetic diagnosis. Nat Genet. 1993 June 01;4(2):160–164.
   PubMed Web of Science ®Google Scholar
• Anderson SL, Coli R, Daly IW, et al. Familial dysautonomia is caused by mutations of the IKAP gene. Am J Hum Genet. 2001 Mar;68(3):753–758.
   PubMed Web of Science ®Google Scholar
• Sinha R, Kim YJ, Nomakuchi T, et al. Antisense oligonucleotides correct the familial dysautonomia splicing defect in IKBKAP transgenic mice. Nucleic Acids Res. 2018;46(10):4833–4844.
   PubMed Web of Science ®Google Scholar
• Farrar MA, Kiernan MC. The genetics of spinal muscular atrophy: progress and challenges. Neurotherapeutics. 2015;12(2):290–302.
   PubMed Web of Science ®Google Scholar
• Lorson CL, Hahnen E, Androphy EJ, et al. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc Nat Acad Sci. 1999;96(11):6307–6311.
   PubMed Web of Science ®Google Scholar
• Hua Y, Vickers TA, Okunola HL, et al. Antisense masking of an hnRNP A1/A2 intronic splicing silencer corrects SMN2 splicing in transgenic mice. Am J Hum Genet. 2008;82(4):834–848.
   PubMed Web of Science ®Google Scholar
• Finkel RS, Chiriboga CA, Vajsar J, et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2016 Dec 17;388(10063):3017–3026.
   PubMed Web of Science ®Google Scholar
• Wang J, Schultz PG, Johnson KA. Mechanistic studies of a small-molecule modulator of SMN2 splicing. Proc Nat Acad Sci. 2018;115(20):E4604–E4612.
   PubMed Web of Science ®Google Scholar
• Ratni H, Scalco RS, Stephan AH. Risdiplam, the first approved small molecule splicing modifier drug as a blueprint for future transformative medicines. ACS Med Chem Lett. 2021 June 10;12(6):874–877.
   PubMed Web of Science ®Google Scholar
• Hofstadler SA, Sannes-Lowery KA, Crooke ST, et al. Multiplexed screening of neutral mass-tagged RNA targets against ligand libraries with electrospray ionization FTICR MS:  a paradigm for high-throughput affinity screening. Anal Chem. 1999 August 01;71(16):3436–3440.
   PubMed Web of Science ®Google Scholar
• Rizvi NF, Howe JA, Nahvi A, et al. Discovery of selective RNA-binding small molecules by affinity-selection mass spectrometry. ACS Chem Biol. 2018 Mar 16;13(3):820–831.
   PubMed Web of Science ®Google Scholar
• Mrksich M. Mass spectrometry of self-assembled monolayers: a new tool for molecular surface science. ACS Nano. 2008;2(1):7–18.
   PubMed Web of Science ®Google Scholar
• Griffey Richard H, Hofstadler Steven A, Sannes-Lowery KA, et al. Determinants of aminoglycoside-binding specificity for rRNA by using mass spectrometry. Proc Nat Acad Sci. 1999 August 31;96(18):10129–10133.
   PubMed Web of Science ®Google Scholar
• Bryan MC, Wong CH. Aminoglycoside array for the high-throughput analysis of small molecule RNA interactions. Tetrahedron Lett. 2004;45(18):3639–3642.
   Web of Science ®Google Scholar
• Sztuba-Solinska J, Shenoy SR, Gareiss P, et al. Identification of biologically active, HIV TAR RNA-binding small molecules using small molecule microarrays. J Am Chem Soc. 2014 June 11;136(23):8402–8410.
   PubMed Web of Science ®Google Scholar
• Disney MD, Labuda LP, Paul DJ, et al. Two-dimensional combinatorial screening identifies specific aminoglycoside−RNA internal loop partners. J Am Chem Soc. 2008 August 01;130(33):11185–11194.
   PubMed Web of Science ®Google Scholar
• Disney MD, Winkelsas AM, Velagapudi SP, et al. Inforna 2.0: a platform for the sequence-based design of small molecules targeting structured RNAs. ACS Chem Biol. 2016 June 17;11(6):1720–1728.
   PubMed Web of Science ®Google Scholar
• Haga CL, Velagapudi SP, Childs-Disney JL, et al. Rapid generation of miRNA inhibitor leads by bioinformatics and efficient high-throughput screening methods. Methods Mol Biol. 2017;1517:179–198.
   PubMedGoogle Scholar
• Wicks SL, Hargrove AE. Fluorescent indicator displacement assays to identify and characterize small molecule interactions with RNA. Methods. 2019;167:3–14.
   PubMed Web of Science ®Google Scholar
• Krishnamurthy M, Schirle NT, Beal PA. Screening helix-threading peptides for RNA binding using a thiazole orange displacement assay. Bioorg Med Chem. 2008;16(19):8914–8921.
   PubMed Web of Science ®Google Scholar
• Asare-Okai PN, Chow CS. A modified fluorescent intercalator displacement assay for RNA ligand discovery. Anal Biochem. 2011;408(2):269–276.
   PubMed Web of Science ®Google Scholar
• Matsumoto C, Hamasaki K, Mihara H, et al. A high-throughput screening utilizing intramolecular fluorescence resonance energy transfer for the discovery of the molecules that bind HIV-1 TAR RNA specifically. Bioorg Med Chem Lett. 2000 Aug 21;10(16):1857–1861.
   PubMed Web of Science ®Google Scholar
• Morley SD, Afshar M. Validation of an empirical RNA-ligand scoring function for fast flexible docking using Ribodock. J Comput Aided Mol Des. 2004 Mar;18(3):189–208.
   PubMed Web of Science ®Google Scholar
• Ruiz-Carmona S, Alvarez-Garcia D, Foloppe N, et al. rDock: a fast, versatile and open source program for docking ligands to proteins and nucleic acids. Plos Comput Biol. 2014;10(4):e1003571–e1003571.
   PubMed Web of Science ®Google Scholar
• Lang PT, Brozell SR, Mukherjee S, et al. DOCK 6: combining techniques to model RNA-small molecule complexes. RNA. 2009;15(6):1219–1230.
   PubMed Web of Science ®Google Scholar
• Li H, Leung K, Wong M, editors. idock: a multithreaded virtual screening tool for flexible ligand docking. 2012 IEEE Symposium on Computational Intelligence in Bioinformatics and Computational Biology (CIBCB); 2012 May 9-12. San Diego, USA; 2012.
   Google Scholar
• Eberhardt J, Santos-Martins D, Tillack AF, et al. AutoDock Vina 1.2.0: new docking methods, expanded force field, and python bindings. J Chem Inf Model. 2021 August 23;61(8):3891–3898.
   PubMed Web of Science ®Google Scholar
• Stefaniak F, Bujnicki JM, Schlick T. Annapurna: a scoring function for predicting RNA-small molecule binding poses. Plos Comput Biol. 2021;17(2):e1008309.
   PubMed Web of Science ®Google Scholar
• Chhabra S, Xie J, Frank AT. RNAPosers: machine learning classifiers for ribonucleic acid–ligand poses.J Phys Chem A. 2020 June 04;124(22):4436–4445.
   Web of Science ®Google Scholar
• Jamal S, Periwal V, Consortium O, et al. Computational analysis and predictive modeling of small molecule modulators of microRNA. J Cheminform. 2012 August 13];4(1):16.
   PubMedGoogle Scholar
• Haga Christopher L. GCN miR-21. 2021 [cited 2022]. Available from: https://github.com/Digital-Chemist/GCN-miR-21
   Google Scholar
• Sun S, Yang J, Zhang Z. RNALigands: a database and web server for RNA-ligand interactions. RNA. 2022 Feb;28(2):115–122.
   PubMed Web of Science ®Google Scholar
• Oliver C, Mallet V, Gendron RS, et al. Augmented base pairing networks encode RNA-small molecule binding preferences. Nucleic Acids Res. 2020 Aug 20;48(14):7690–7699.
   PubMed Web of Science ®Google Scholar
• Haga Christopher L. A pharmacophore-based deep learning model for identifying RNA ligands 2022. Available from: https://github.com/Digital-Chemist/PhaRNA.ai
   Google Scholar