Skip to main content

Recognition of RNA Sequence and Structure by Duplex and Triplex Formation: Targeting miRNA and Pre-miRNA

  • Chapter
  • First Online:

Part of the book series: RNA Technologies ((RNATECHN))

Abstract

RNAs form complex structures containing both single-stranded (ss) and double-stranded (ds) regions for their diverse regulatory and catalytic functions. The emerging RNA sequence and structure databases provide the foundation for developing RNA-binding ligands for reprogramming RNA–RNA and RNA–protein interactions through the recognition of RNA sequence and structure. We choose miRNA biogenesis and gene regulation pathways as examples to summarize how chemically modified nucleic acid oligomers can be used to target specific RNA sequences and structures through duplex and triplex formation. We discuss the significant progress that has been made in using anti-miRNA oligonucleotides in targeting mature miRNA by duplex formation. The strategy of targeting dsRNA by triplex formation is relatively less explored. We summarize the recent results of developing nucleobase and backbone modifications in peptide nucleic acids (PNAs) to facilitate structure-specific and selective targeting of dsRNAs over ssRNA and dsDNA at physiological conditions. We briefly discuss how sequence-specific dsRNA-binding PNAs may be utilized to target disease-associated miRNA precursors and viral RNAs.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Abes S, Turner JJ, Ivanova GD et al (2007) Efficient splicing correction by PNA conjugation to an R6-Penetratin delivery peptide. Nucleic Acids Res 35:4495–4502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ahn DG, Kourakis MJ, Rohde LA et al (2002) T-box gene tbx5 is essential for formation of the pectoral limb bud. Nature 417:754–758

    Article  CAS  PubMed  Google Scholar 

  • Amato F, Tomaiuolo R, Nici F et al (2014) Exploitation of a very small peptide nucleic acid as a new inhibitor of miR-509-3p involved in the regulation of cystic fibrosis disease gene expression. Biomed Res Int 2014:610718

    Article  PubMed  PubMed Central  Google Scholar 

  • Aupeix K, Le Tinévez R, Toulmé J-J (1999) Binding of oligopyrimidines to the RNA hairpin responsible for the ribosome gag-pol frameshift in HIV-1. FEBS Lett 449:169–174

    Article  CAS  PubMed  Google Scholar 

  • Avitabile C, Saviano M, D’Andrea L et al (2012) Targeting pre-miRNA by peptide nucleic acids: a new strategy to interfere in the miRNA maturation. Artif DNA PNA XNA 3:88–96

    Article  PubMed  PubMed Central  Google Scholar 

  • Avitabile C, Cimmino A, Romanelli A (2014) Oligonucleotide analogues as modulators of the expression and function of noncoding RNAs (ncRNAs): emerging therapeutics applications. J Med Chem 57:10220–10240

    Article  CAS  PubMed  Google Scholar 

  • Avitabile C, Accardo A, Ringhieri P et al (2015) Incorporation of naked peptide nucleic acids into liposomes leads to fast and efficient delivery. Bioconjugate Chem 26:1533–1541

    Article  CAS  Google Scholar 

  • Benner SA (2004) Understanding nucleic acids using synthetic chemistry. Acc Chem Res 37:784–797

    Article  CAS  PubMed  Google Scholar 

  • Boisguérin P, Deshayes S, Gait MJ et al (2015) Delivery of therapeutic oligonucleotides with cell penetrating peptides. Adv Drug Del Rev 87:52–67

    Article  CAS  Google Scholar 

  • Bose D, Jayaraj G, Suryawanshi H et al (2012) 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

    Article  CAS  Google Scholar 

  • Bose D, Nahar S, Rai MK et al (2015a) Selective inhibition of miR-21 by phage display screened peptide. Nucleic Acids Res 43:4342–4352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bose T, Banerjee A, Nahar S et al (2015b) β,γ-Bis-substituted PNA with configurational and conformational switch: preferred binding to cDNA/RNA and cell-uptake studies. Chem Commun 51:7693–7696

    Article  CAS  Google Scholar 

  • Buchardt O, Egholm M, Berg RH et al (1993) Peptide nucleic acids and their potential applications in biotechnology. Trends Biotechnol 11:384–386

    Article  CAS  PubMed  Google Scholar 

  • Buchini S, Leumann CJ (2004) Stable and selective recognition of three base pairs in the parallel triple-helical DNA binding motif. Angew Chem Int Ed 43:3925–3928

    Article  CAS  Google Scholar 

  • Cao S-Q, Okamoto I, Tsunoda H et al (2011) Synthesis and triplex-forming properties of oligonucleotides containing thio-substituted C-nucleoside 4-thiopseudoisocytidine. Tetrahedron Lett 52:407–410

    Article  CAS  Google Scholar 

  • Cartegni L, Krainer AR (2003) Correction of disease-associated exon skipping by synthetic exon-specific activators. Nat Struct Biol 10:120–125

    Article  CAS  PubMed  Google Scholar 

  • Cassidy SA, Slickers P, Trent JO et al (1997) Recognition of GC base pairs by triplex forming oligonucleotides containing nucleosides derived from 2-aminopyridine. Nucleic Acids Res 25:4891–4898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cech TR, Steitz JA (2014) The noncoding RNA revolution—trashing old rules to forge new ones. Cell 157:77–94

    Article  CAS  PubMed  Google Scholar 

  • Chan JA, Krichevsky AM, Kosik KS (2005) MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 65:6029–6033

    Article  CAS  PubMed  Google Scholar 

  • Chen DL, McLaughlin LW (2000) Use of pK a differences to enhance the formation of base triplets involving C−G and G−C base pairs. J Org Chem 65:7468–7474

    Article  CAS  PubMed  Google Scholar 

  • Cheng CJ, Saltzman WM (2012) Polymer nanoparticle-mediated delivery of microRNA inhibition and alternative splicing. Mol Pharm 9:1481–1488

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng CJ, Bahal R, Babar IA et al (2015) MicroRNA silencing for cancer therapy targeted to the tumour microenvironment. Nature 518:107–110

    Article  CAS  PubMed  Google Scholar 

  • Chenoweth DM, Meier JL, Dervan PB (2013) Pyrrole-imidazole polyamides distinguish between double-helical DNA and RNA. Angew Chem Int Ed 52:415–418

    Article  CAS  Google Scholar 

  • Chirayil S, Chirayil R, Luebke KJ (2009) Discovering ligands for a microRNA precursor with peptoid microarrays. Nucleic Acids Res 37:5486–5497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Conrad NK (2014) The emerging role of triple helices in RNA biology. Wiley Interdiscip Rev RNA 5:15–29

    Article  CAS  PubMed  Google Scholar 

  • Corradini R, Sforza S, Tedeschi T et al (2011) Peptide nucleic acids with a structurally biased backbone: updated review and emerging challenges. Curr Top Med Chem 11:1535–1554

    Article  CAS  PubMed  Google Scholar 

  • Crooke ST, Geary RS (2013) Clinical pharmacological properties of mipomersen (Kynamro), a second generation antisense inhibitor of apolipoprotein B. Br J Clin Pharmacol 76:269–276

    Article  CAS  PubMed  Google Scholar 

  • Cummins LL, Owens SR, Risen LM et al (1995) Characterization of fully 2′-modified oligoribonucleotide hetero- and homoduplex hybridization and nuclease sensitivity. Nucleic Acids Res 23:2019–2024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Das I, Désiré J, Manvar D et al (2012) A peptide nucleic acid–aminosugar conjugate targeting transactivation response element of HIV-1 RNA genome shows a high bioavailability in human cells and strongly inhibits Tat-mediated transactivation of HIV-1 transcription. J Med Chem 55:6021–6032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Davis S, Lollo B, Freier S et al (2006) Improved targeting of miRNA with antisense oligonucleotides. Nucleic Acids Res 34:2294–2304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Devi G, Yuan Z, Lu Y et al (2014) Incorporation of thio-pseudoisocytosine into triplex-forming peptide nucleic acids for enhanced recognition of RNA duplexes. Nucleic Acids Res 42:4008–4018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Devi G, Zhou Y, Zhong Z et al (2015) RNA triplexes: from structural principles to biological and biotech applications. Wiley Interdiscip Rev RNA 6:111–128

    Article  CAS  PubMed  Google Scholar 

  • Dragulescu-Andrasi A, Zhou P, He G et al (2005) Cell-permeable GPNA with appropriate backbone stereochemistry and spacing binds sequence-specifically to RNA. Chem Commun 2005:244–246

    Article  CAS  Google Scholar 

  • Egholm M, Christensen L, Dueholm KL et al (1995) Efficient pH-independent sequence-specific DNA binding by pseudoisocytosine-containing bis-PNA. Nucleic Acids Res 23:217–222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eldrup AB, Dahl O, Nielsen PE (1997) A novel peptide nucleic acid monomer for recognition of thymine in triple-helix structures. J Am Chem Soc 119:11116–11117

    Article  CAS  Google Scholar 

  • Esau C, Davis S, Murray SF et al (2006) miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab 3:87–98

    Article  CAS  PubMed  Google Scholar 

  • Fabani MM, Gait MJ (2008) miR-122 targeting with LNA/2′-O-methyl oligonucleotide mixmers, peptide nucleic acids (PNA), and PNA–peptide conjugates. RNA 14:336–346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fabani MM, Abreu-Goodger C, Williams D et al (2010) Efficient inhibition of miR-155 function in vivo by peptide nucleic acids. Nucleic Acids Res 38:4466–4475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Faria M, Spiller DG, Dubertret C et al (2001) Phosphoramidate oligonucleotides as potent antisense molecules in cells and in vivo. Nat Biotechol 19:40–44

    Article  CAS  Google Scholar 

  • Feng Y, Zhang X, Graves P et al (2012) A comprehensive analysis of precursor microRNA cleavage by human Dicer. RNA 18:2083–2092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fletcher S, Honeyman K, Fall AM et al (2007) Morpholino oligomer-mediated exon skipping averts the onset of dystrophic pathology in the mdx mouse. Mol Ther 15:1587–1592

    Article  CAS  PubMed  Google Scholar 

  • Gaglione M, Milano G, Chambery A et al (2011) PNA-based artificial nucleases as antisense and anti-miRNA oligonucleotide agents. Mol Biosyst 7:2490–2499

    Article  CAS  PubMed  Google Scholar 

  • Gambari R (2014) Peptide nucleic acids: a review on recent patents and technology transfer. Expert Opin Ther Pat 24:267–294

    Article  CAS  PubMed  Google Scholar 

  • Ge J, Yu YT (2013) RNA pseudouridylation: new insights into an old modification. Trends Biochem Sci 38:210–218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geary R, Henry S, Grillone L (2002) Fomivirsen. Clin Pharmacokinet 41:255–260

    Article  CAS  PubMed  Google Scholar 

  • Gebert LF, Rebhan MA, Crivelli SE et al (2014) Miravirsen (SPC3649) can inhibit the biogenesis of miR-122. Nucleic Acids Res 42:609–621

    Article  CAS  PubMed  Google Scholar 

  • Gelsinger C, Steinhagen-Thiessen E, Kassner U (2012) Therapeutic potential of Mipomersen in the management of familial hypercholesterolaemia. Drugs 72:1445–1455

    Article  CAS  PubMed  Google Scholar 

  • Gumireddy K, Young DD, Xiong X et al (2008) Small-molecule inhibitors of microRNA miR-21 function. Angew Chem Int Ed 47:7482–7484

    Article  CAS  Google Scholar 

  • Gupta P, Zengeya T, Rozners E (2011) Triple helical recognition of pyrimidine inversions in polypurine tracts of RNA by nucleobase-modified PNA. Chem Commun 47:11125–11127

    Article  CAS  Google Scholar 

  • Gupta P, Muse O, Rozners E (2012) Recognition of double-stranded RNA by guanidine-modified peptide nucleic acids. Biochemistry 51:63–73

    Article  CAS  PubMed  Google Scholar 

  • Hansen ME, Bentin T, Nielsen PE (2009) High-affinity triplex targeting of double stranded DNA using chemically modified peptide nucleic acid oligomers. Nucleic Acids Res 37:4498–4507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hildbrand S, Blaser A, Parel SP et al (1997) 5-Substituted 2-aminopyridine C-nucleosides as protonated cytidine equivalents: increasing efficiency and selectivity in DNA triple-helix formation. J Am Chem Soc 119:5499–5511

    Article  CAS  Google Scholar 

  • Holmes SC, Arzumanov AA, Gait MJ (2003) Steric inhibition of human immunodeficiency virus type-1 Tat-dependent trans-activation in vitro and in cells by oligonucleotides containing 2′-O-methyl G-clamp ribonucleoside analogues. Nucleic Acids Res 31:2759–2768

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang X-W, Pan J, An X-Y et al (2007) Inhibition of bacterial translation and growth by peptide nucleic acids targeted to domain II of 23S rRNA. J Pept Sci 13:220–226

    Article  CAS  Google Scholar 

  • Hutvagner G, Simard MJ, Mello CC et al (2004) Sequence-specific inhibition of small RNA function. PLoS Biol 2, E98

    Article  PubMed  PubMed Central  Google Scholar 

  • Järver P, Torres AG, Gait MJ (2014) Synthetic microRNA blocking agents. In: Arbuthnot P, Weinberg MS (eds) Applied RNAi: from fundamental research to therapeutic applications. Caister Academic Press, Norfolk, pp 105–126

    Google Scholar 

  • Jayaraj GG, Nahar S, Maiti S (2015) Nonconventional chemical inhibitors of microRNA: therapeutic scope. Chem Commun 51:820–831

    Article  CAS  Google Scholar 

  • Jeker LT, Marone R (2015) Targeting microRNAs for immunomodulation. Curr Opin Pharmacol 23:25–31

    Article  CAS  PubMed  Google Scholar 

  • Kan L-S, Lin WC, Yadav RD et al (1999) NMR studies of the tautomerism in pseudoisocytidine. Nucleosides Nucleotides 18:1091–1093

    Article  CAS  Google Scholar 

  • Kawasaki AM, Casper MD, Freier SM et al (1993) Uniformly modified 2′-deoxy-2′-fluoro phosphorothioate oligonucleotides as nuclease-resistant antisense compounds with high affinity and specificity for RNA targets. J Med Chem 36:831–841

    Article  CAS  PubMed  Google Scholar 

  • Kierzek E, Ciesielska A, Pasternak K et al (2005) The influence of locked nucleic acid residues on the thermodynamic properties of 2′-O-methyl RNA/RNA heteroduplexes. Nucleic Acids Res 33:5082–5093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kloosterman WP, Lagendijk AK, Ketting RF et al (2007) Targeted inhibition of miRNA maturation with morpholinos reveals a role for miR-375 in pancreatic islet development. PLoS Biol 5, e203

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Koppelhus U, Zachar V, Nielsen PE et al (1997) Efficient in vitro inhibition of HIV-1 gag reverse transcription by peptide nucleic acid (PNA) at minimal ratios of PNA/RNA. Nucleic Acids Res 25:2167–2173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krutzfeldt J, Rajewsky N, Braich R et al (2005) Silencing of microRNAs in vivo with ‘antagomirs’. Nature 438:685–689

    Article  PubMed  CAS  Google Scholar 

  • Kurakin A, Jakob Larsen H, Nielsen PE (1998) Cooperative strand displacement by peptide nucleic acid (PNA). Chem Biol 5:81–89

    Article  CAS  PubMed  Google Scholar 

  • Lamond AI, Sproat BS (1993) Antisense oligonucleotides made of 2′-O-alkyl RNA: their properties and applications in RNA biochemistry. FEBS Lett 325:123–127

    Article  CAS  PubMed  Google Scholar 

  • Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854

    Article  CAS  PubMed  Google Scholar 

  • Lennox KA, Behlke MA (2010) A direct comparison of anti-microRNA oligonucleotide potency. Pharm Res 27:1788–1799

    Article  CAS  PubMed  Google Scholar 

  • Lennox KA, Owczarzy R, Thomas DM et al (2013) Improved performance of anti-miRNA oligonucleotides using a novel non-nucleotide modifier. Mol Ther Nucleic Acids 2, e117

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li Z, Rana TM (2014) Therapeutic targeting of microRNAs: current status and future challenges. Nat Rev Drug Discov 13:622–638

    Article  CAS  PubMed  Google Scholar 

  • Li M, Zengeya T, Rozners E (2010) Short peptide nucleic acids bind strongly to homopurine tract of double helical RNA at pH 5.5. J Am Chem Soc 132:8676–8681

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li N, You X, Chen T et al (2013) Global profiling of miRNAs and the hairpin precursors: insights into miRNA processing and novel miRNA discovery. Nucleic Acids Res 41:3619–3634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lindow M, Kauppinen S (2012) Discovering the first microRNA-targeted drug. J Cell Biol 199:407–412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu YP, Schopman NC, Berkhout B (2013) Dicer-independent processing of short hairpin RNAs. Nucleic Acids Res 41:3723–3733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma X, Devi G, Qu Q et al (2014) Intracellular delivery of antisense peptide nucleic acid by fluorescent mesoporous silica nanoparticles. Bioconjugate Chem 25:1412–1420

    Article  CAS  Google Scholar 

  • Majlessi M, Nelson NC, Becker MM (1998) Advantages of 2′-O-methyl oligoribonucleotide probes for detecting RNA targets. Nucleic Acids Res 26:2224–2229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Manicardi A, Fabbri E, Tedeschi T et al (2012) Cellular uptakes, biostabilities and anti-miR-210 activities of chiral arginine-PNAs in leukaemic K562 cells. ChemBioChem 13:1327–1337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Manoharan M (1999) 2′-Carbohydrate modifications in antisense oligonucleotide therapy: importance of conformation, configuration and conjugation. Biochim Biophys Acta 1489:117–130

    Article  CAS  PubMed  Google Scholar 

  • Meister G, Landthaler M, Dorsett Y et al (2004) Sequence-specific inhibition of microRNA- and siRNA-induced RNA silencing. RNA 10:544–550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mendell JR, Rodino-Klapac LR, Sahenk Z et al (2013) Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol 74:637–647

    Article  CAS  PubMed  Google Scholar 

  • Mitra R, Ganesh KN (2012) Aminomethylene peptide nucleic acid (am-PNA): synthesis, regio-/stereospecific DNA binding, and differential cell uptake of (α/γ, R/S)am-PNA analogues. J Org Chem 77:5696–5704

    Article  CAS  PubMed  Google Scholar 

  • Miyata K, Tamamushi R, Tsunoda H et al (2009) Synthesis and triplex formation of oligonucleotides containing 8-thioxodeoxyadenosine. Org Lett 11:605–608

    Article  CAS  PubMed  Google Scholar 

  • Moens U (2009) Silencing viral microRNA as a novel antiviral therapy? J Biomed Biotechnol 2009:419539

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Muse O, Zengeya T, Mwaura J et al (2013) Sequence selective recognition of double-stranded RNA at physiologically relevant conditions using PNA-peptide conjugates. ACS Chem Biol 8:1683–1686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nair JK, Willoughby JL, Chan A et al (2014) Multivalent N-acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits robust RNAi-mediated gene silencing. J Am Chem Soc 136:16958–16961

    Article  CAS  PubMed  Google Scholar 

  • Ng EW, Shima DT, Calias P et al (2006) Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nat Rev Drug Discov 5:123–132

    Article  CAS  PubMed  Google Scholar 

  • Nielsen PE, Egholm M (1999) An introduction to peptide nucleic acid. Curr Issues Mol Biol 1:89–104

    CAS  PubMed  Google Scholar 

  • Nielsen PE, Egholm M, Berg RH et al (1991) Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide. Science 254:1497–1500

    Article  CAS  PubMed  Google Scholar 

  • Nikolova EN, Zhou H, Gottardo FL et al (2013) A historical account of Hoogsteen base-pairs in duplex DNA. Biopolymers 99:955–968

    CAS  PubMed  Google Scholar 

  • Obad S, dos Santos CO, Petri A et al (2011) Silencing of microRNA families by seed-targeting tiny LNAs. Nat Genet 43:371–378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oh S, Ju Y, Park H (2009) A highly effective and long-lasting inhibition of miRNAs with PNA-based antisense oligonucleotides. Mol Cells 28:341–345

    Article  CAS  PubMed  Google Scholar 

  • Oh SY, Ju Y, Kim S et al (2010) PNA-based antisense oligonucleotides for microRNAs inhibition in the absence of a transfection reagent. Oligonucleotides 20:225–230

    Article  CAS  PubMed  Google Scholar 

  • Okamoto I, Seio K, Sekine M (2006) Triplex forming ability of oligonucleotides containing 2′-O-methyl-2-thiouridine or 2-thiothymidine. Bioorg Med Chem Lett 16:3334–3336

    Article  CAS  PubMed  Google Scholar 

  • Ono A, Ts’o POP, Kan LS (1991) Triplex formation of oligonucleotides containing 2′-O-methylpseudoisocytidine in substitution for 2′-deoxycytidine. J Am Chem Soc 113:4032–4033

    Article  CAS  Google Scholar 

  • Ottosen S, Parsley TB, Yang L et al (2015) In vitro antiviral activity and preclinical and clinical resistance profile of miravirsen, a novel anti-hepatitis C virus therapeutic targeting the human factor miR-122. Antimicrob Agents Chemother 59:599–608

    Article  PubMed  CAS  Google Scholar 

  • Panyutin IG, Onyshchenko MI, Englund EA et al (2012) Targeting DNA G-quadruplex structures with peptide nucleic acids. Curr Pharm Des 18:1984–1991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Penna E, Orso F, Taverna D (2015) miR-214 as a key hub that controls cancer networks: small player, multiple functions. J Invest Dermatol 135:960–969

    Article  CAS  PubMed  Google Scholar 

  • Piva R, Spandidos DA, Gambari R (2013) From microRNA functions to microRNA therapeutics: novel targets and novel drugs in breast cancer research and treatment. Int J Oncol 43:985–994

    CAS  PubMed  PubMed Central  Google Scholar 

  • Püschl A, Sforza S, Haaima G et al (1998) Peptide nucleic acids (PNAs) with a functional backbone. Tetrahedron Lett 39:4707–4710

    Article  Google Scholar 

  • Qi L, Chan TH, Tenen DG et al (2014) RNA editome imbalance in hepatocellular carcinoma. Cancer Res 74:1301–1306

    Article  CAS  PubMed  Google Scholar 

  • Ranasinghe RT, Rusling DA, Powers VEC et al (2005) Recognition of CG inversions in DNA triple helices by methylated 3H-pyrrolo [2,3-d] pyrimidin-2(7H)-one nucleoside analogues. Chem Commun 2005:2555–2557

    Article  CAS  Google Scholar 

  • Riguet E, Tripathi S, Chaubey B et al (2004) A peptide nucleic acid-neamine conjugate that targets and cleaves HIV-1 TAR RNA inhibits viral replication. J Med Chem 47:4806–4809

    Article  CAS  PubMed  Google Scholar 

  • Rozners E (2014) Sequence-selective recognition of double-stranded RNA. In: Erdmann VA, Markiewicz WT, Barciszewski J (eds) Chemical biology of nucleic acids, vol 10. Springer Berlin, Heidelberg, pp 167–180

    Chapter  Google Scholar 

  • Rusling DA, Powers VEC, Ranasinghe RT et al (2005) Four base recognition by triplex-forming oligonucleotides at physiological pH. Nucleic Acids Res 33:3025–3032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sacui I, Hsieh W-C, Manna A et al (2015) Gamma peptide nucleic acids: as orthogonal nucleic acid recognition codes for organizing molecular self-assembly. J Am Chem Soc 137:8603–8610

    Article  CAS  PubMed  Google Scholar 

  • Sahu B, Chenna V, Lathrop KL et al (2009) Synthesis of conformationally preorganized and cell-permeable guanidine-based γ-peptide nucleic acids (γGPNAs). J Org Chem 74:1509–1516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Semenyuk A, Darian E, Liu J et al (2010) Targeting of an interrupted polypurine:polypyrimidine sequence in mammalian cells by a triplex-forming oligonucleotide containing a novel base analogue. Biochemistry 49:7867–7878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sharma VK, Sharma RK, Singh SK (2014) Antisense oligonucleotides: modifications and clinical trials. Med Chem Commun 5:1454–1471

    Article  CAS  Google Scholar 

  • Shibata C, Otsuka M, Kishikawa T et al (2013) Current status of miRNA-targeting therapeutics and preclinical studies against gastroenterological carcinoma. Mol Cell Ther 1:5

    Article  PubMed  PubMed Central  Google Scholar 

  • Shiraishi T, Nielsen PE (2014) Cellular delivery of peptide nucleic acids (PNAs). Methods Mol Biol 1050:193–205

    Article  CAS  PubMed  Google Scholar 

  • Shortridge MD, Varani G (2015) Structure based approaches for targeting non-coding RNAs with small molecules. Curr Opin Struct Biol 30:79–88

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simonson B, Das S (2015) MicroRNA therapeutics: the next magic bullet? Mini Rev Med Chem 15:467–474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Starega-Roslan J, Koscianska E, Kozlowski P et al (2011) The role of the precursor structure in the biogenesis of microRNA. Cell Mol Life Sci 68:2859–2871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stein CA, Hansen JB, Lai J et al (2010) Efficient gene silencing by delivery of locked nucleic acid antisense oligonucleotides, unassisted by transfection reagents. Nucleic Acids Res 38, e3

    Article  CAS  PubMed  Google Scholar 

  • Strobel SA, Cochrane JC (2007) RNA catalysis: ribozymes, ribosomes, and riboswitches. Curr Opin Chem Biol 11:636–643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suwanmanee T, Sierakowska H, Fucharoen S et al (2002) Repair of a splicing defect in erythroid cells from patients with beta-thalassemia/HbE disorder. Mol Ther 6:718–726

    Article  CAS  PubMed  Google Scholar 

  • Toh D-FK, Devi G, Patil KM et al (2016) Incorporating a guanidine-modified cytosine base into triplex-forming PNAs for the recognition of a C-G pyrimidine-purine inversion site of an RNA duplex. Nucleic Acids Res, Submitted

    Google Scholar 

  • Torres AG, Fabani MM, Vigorito E et al (2011a) MicroRNA fate upon targeting with anti-miRNA oligonucleotides as revealed by an improved Northern-blot-based method for miRNA detection. RNA 17:933–943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Torres AG, Threlfall RN, Gait MJ (2011b) Potent and sustained cellular inhibition of miR-122 by lysine-derivatized peptide nucleic acids (PNA) and phosphorothioate locked nucleic acid (LNA)/2′-O-methyl (OMe) mixmer anti-miRs in the absence of transfection agents. Artif DNA: PNA XNA 2:71–78

    Article  Google Scholar 

  • Torres AG, Fabani MM, Vigorito E et al (2012) Chemical structure requirements and cellular targeting of microRNA-122 by peptide nucleic acids anti-miRs. Nucleic Acids Res 40:2152–2167

    Article  CAS  PubMed  Google Scholar 

  • Turner JJ, Ivanova GD, Verbeure B et al (2005) Cell-penetrating peptide conjugates of peptide nucleic acids (PNA) as inhibitors of HIV-1 Tat-dependent trans-activation in cells. Nucleic Acids Res 33:6837–6849

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tycowski KT, Guo YE, Lee N et al (2015) Viral noncoding RNAs: more surprises. Genes Dev 29:567–584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van Rooij E, Kauppinen S (2014) Development of microRNA therapeutics is coming of age. EMBO Mol Med 6:851–864

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Velagapudi SP, Vummidi BR, Disney MD (2015) Small molecule chemical probes of microRNA function. Curr Opin Chem Biol 24:97–103

    Article  CAS  PubMed  Google Scholar 

  • Verma S, Eckstein F (1998) Modified oligonucleotides: synthesis and strategy for users. Annu Rev Biochem 67:99–134

    Article  CAS  PubMed  Google Scholar 

  • Voit T, Topaloglu H, Straub V et al (2014) Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study. Lancet Neurol 13:987–996

    Article  CAS  PubMed  Google Scholar 

  • von Krosigk U, Benner SA (1995) pH-independent triple helix formation by an oligonucleotide containing a pyrazine donor-donor-acceptor base. J Am Chem Soc 117:5361–5362

    Article  Google Scholar 

  • Wang G, Xu XS (2004) Peptide nucleic acid (PNA) binding-mediated gene regulation. Cell Res 14:111–116

    Article  PubMed  Google Scholar 

  • Wexselblatt E, Esko JD, Tor Y (2014) On guanidinium and cellular uptake. J Org Chem 79:6766–6774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wightman B, Ha I, Ruvkun G (1993) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75:855–862

    Article  CAS  PubMed  Google Scholar 

  • Wilson RC, Doudna JA (2013) Molecular mechanisms of RNA interference. Annu Rev Biophys 42:217–239

    Article  CAS  PubMed  Google Scholar 

  • Xiang G, Soussou W, McLaughlin LW (1994) A new pyrimidine nucleoside (m5oxC) for the pH-independent recognition of G-C base pairs by oligonucleotide-directed triplex formation. J Am Chem Soc 116:11155–11156

    Article  CAS  Google Scholar 

  • Xiang G, Bogacki R, McLaughlin LW (1996) Use of a pyrimidine nucleoside that functions as a bidentate hydrogen bond donor for the recognition of isolated or contiguous G-C base pairs by oligonucleotide-directed triplex formation. Nucleic Acids Res 24:1963–1970

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang W, Chendrimada TP, Wang Q et al (2006) Modulation of microRNA processing and expression through RNA editing by ADAR deaminases. Nat Struct Mol Biol 13:13–21

    Article  CAS  PubMed  Google Scholar 

  • Yaroslavsky Anastasia I, Smolina Irina V (2013) Fluorescence imaging of single-copy DNA sequences within the human genome using PNA-directed padlock probe assembly. Chem Biol 20:445–453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yue Y, Liu J, He C (2015) RNA N 6-methyladenosine methylation in post-transcriptional gene expression regulation. Genes Dev 29:1343–1355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zengeya T, Li M, Rozners E (2011) PNA containing isocytidine nucleobase: synthesis and recognition of double helical RNA. Bioorg Med Chem Lett 21:2121–2124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zengeya T, Gupta P, Rozners E (2012) Triple-helical recognition of RNA using 2-aminopyridine-modified PNA at physiologically relevant conditions. Angew Chem Int Ed 51:12593–12596

    Article  CAS  Google Scholar 

  • Zengeya T, Gindin A, Rozners E (2013) Improvement of sequence selectivity in triple helical recognition of RNA by phenylalanine-derived PNA. Artif DNA: PNA XNA 4:69–76

    Article  Google Scholar 

  • Zhou P, Wang M, Du L et al (2003) Novel binding and efficient cellular uptake of guanidine-based peptide nucleic acids (GPNA). J Am Chem Soc 125:6878–6879

    Article  CAS  PubMed  Google Scholar 

  • Zhou P, Dragulescu-Andrasi A, Bhattacharya B et al (2006) Synthesis of cell-permeable peptide nucleic acids and characterization of their hybridization and uptake properties. Bioorg Med Chem Lett 16:4931–4935

    Article  CAS  PubMed  Google Scholar 

  • Zhou Y, Kierzek E, Loo ZP et al (2013) Recognition of RNA duplexes by chemically modified triplex-forming oligonucleotides. Nucleic Acids Res 41:6664–6673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zipeto MA, Jiang Q, Melese E et al (2015) RNA rewriting, recoding, and rewiring in human disease. Trends Mol Med 21:549–559

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Prof Mike Gait, Prof Xavier Roca, Prof Ding Xiang Liu, Prof Sek-Man Wong, Dr Jiazi Tan, and Prof Souvik Maiti and his group members for critically reading the manuscript. This work was supported by Singapore Ministry of Education Tier 2 research grants MOE2013-T2-2-024 and MOE2015-T2-1-028 to GC.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gang Chen .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Patil, K.M., Chen, G. (2016). Recognition of RNA Sequence and Structure by Duplex and Triplex Formation: Targeting miRNA and Pre-miRNA. In: Jurga, S., Erdmann (Deceased), V., Barciszewski, J. (eds) Modified Nucleic Acids in Biology and Medicine. RNA Technologies. Springer, Cham. https://doi.org/10.1007/978-3-319-34175-0_13

Download citation

Publish with us

Policies and ethics