Overview of RNA G-quadruplex structures
Abstract
G-quadruplexes are non-canonical secondary structures which may be formed by guanine rich sequences, both in vitro and in living cells. The number of biological functions assigned to these structural motifs has grown rapidly since the discovery of their involvement in the telomere maintenance. Knowledge of the three-dimensional structures of G-quadruplexes plays an important role in understanding their conformational diversity, physiological functions, and in the design of novel drugs targeting G-quadruplexes. For the last decades, structural studies have been mainly focused on the DNA G-quadruplexes. Their RNA counterparts gained an increased interest along with still-emerging recognition of the central role of RNA in multiple cellular processes. In this review we focus on structural properties of RNA G-quadruplexes, based on high-resolution structures, available in RCSB PDB data base and on structural models. In addition, we point out to the current challenges in this field of research.
References
Adrian M, Heddi B, Phan A. T, (2012) NMR Spectroscopy of G-Quadruplexes. Methods 57: 11–24. doi:10.1016/j.ymeth.2012.05.003
Agarwala P, Pandey S, Maiti S, (2015) The Tale of RNA G-Quadruplex. Org. Biomol. Chem. 13: 5570–5585. doi:10.1039/C4OB02681K
Ambrus A, Chen D, Dai J, Bialis T, Jones R, Yang D, (2006) Human Telomeric Sequence Forms a Hybrid-Type Intramolecular G-Quadruplex Structure with Mixed Parallel/antiparallel Strands in Potassium Solution. Nucleic Acids Research 34: 2723–2735. doi:10.1093/nar/gkl348
Awang G, Sen D, (1993) Mode of Dimerization of HIV-1 Genomic RNA. Biochemistry 32: 11453–11457. doi:10.1021/bi00093a024
Azzalin, Claus M, Reichenbach P, Khoriauli L, Giulotto E, Lingner J, (2007) Telomeric Repeat Containing RNA and RNA Surveillance Factors at
Mammalian Chromosome Ends. Science 318: 798–801. doi:10.1126/science.1147182
Balasubramanian S, Neidle S, (2009) G-Quadruplex Nucleic Acids as Therapeutic Targets. Current Opinion in Chemical Biology 13: 345–353. doi:10.1016/j.cbpa.2009.04.637
Biffi G, Tannahill D, McCafferty J, Balasubramanian S (2013) Quantitative Visualization of DNA G-Quadruplex Structures in Human Cells Nature Chemistry 5: 182–186. doi:10.1038/nchem.1548
Biffi G, Antonio M Di, Tannahill D, Balasubramanian S, (2014) Visualization and Selective Chemical Targeting of RNA G-Quadruplex Structures in the Cytoplasm of Human Cells Nature Chemistry 6: 75–80. doi:10.1038/nchem.1805
Bugaut A, Rodriguez R, Kumari S, Hsu STD, Balasubramanian S, (2010) Small Molecule-Mediated Inhibition of Translation by Targeting a Native RNA G-Quadruplex Organic & Biomolecular Chemistry 8: 2771-2776. doi:10.1039/c002418j
Burge S, Parkinson GN, Hazel P, Todd AK, Neidle S (2006) Quadruplex DNA: Sequence, Topology and Structure Nucleic Acids Research 34: 5402–5415. doi:10.1093/nar/gkl655
Cahoon, LA, Seifert HS, (2009) An Alternative DNA Structure Is Necessary for Pilin Antigenic Variation in Neisseria Gonorrhoeae. Science 325: 764–767. doi:10.1126/science.1175653
Campbell NH, Parkinson GN, (2007) Crystallographic Studies of Quadruplex Nucleic Acids Methods 43: 252–263. doi:10.1016/j.ymeth.2007.08.005
Campbell NH, Collie GW, Neidle S (2012) Crystallography of DNA and RNA G-Quadruplex Nucleic Acids and Their Ligand Complexes Current Protocols in Nucleic Acid Chemistry Chapter 17: Unit17.6. doi:10.1002/0471142700.nc1706s50
Cheong C, Moore PB, (1992) Solution Structure of an Unusually Stable RNA Tetraplex Containing G- and U-Quartet Structures Biochemistry 31: 8406–8414. doi:10.1021/bi00151a003
Collie GW, Parkinson GN (2011) The Application of DNA and RNA G-Quadruplexes to Therapeutic Medicines. Chemical Society Reviews 40: 5867–5892. doi:10.1039/c1cs15067g
Collie GW, Sparapani S, Parkinson GN, Neidle S, (2011) Structural Basis of Telomeric RNA Quadruplex–Acridine Ligand Recognition. Journal of the American Chemical Society 133: 2721–2728. doi:10.1021/ja109767y
Deng, J, Xiong Y, Sundaralingam M, (2001) X-Ray Analysis of an RNA Tetraplex (UGGGGU)4 with Divalent Sr2+ Ions at Subatomic Resolution (0.61 Å). Proceedings of the National Academy of Sciences of the United States of America 98: 13665–13670. doi:10.1073/pnas.241374798
Deng Z, Norseen J, Wiedmer A, Riethman H, Lieberman PM, (2009) TERRA RNA Binding to TRF2 Facilitates Heterochromatin Formation and ORC Recruitment at Telomeres. Molecular Cell 35: 403–413. doi:10.1016/j.molcel.2009.06.025
Di Antonio M, Biffi G, Mariani A, Raiber EA, Rodriguez R, Balasubramanian S (2012) Selective RNA Versus DNA G-Quadruplex Targeting by In Situ Click Chemistry. Angewandte Chemie International Edition 51: 11073–11078. doi:10.1002/anie.201206281
Eddy J, Maizels N, (2007) Conserved Elements with Potential to Form Polymorphic G-Quadruplex Structures in the First Intron of Human Genes. Nucleic Acids Research 36: 1321–1333. doi:10.1093/nar/gkm1138
Faudale M, Cogoi S, Xodo L. E, (2012) Photoactivated Cationic Alkyl-Substituted Porphyrin Binding to g4-RNA in the 5′-UTR of KRAS Oncogene Represses Translation. Chemical Communications. 48: 874–876. doi:10.1039/C1CC15850C
Fyfe AC, Dunten PW, Martick MM, Scott WG (2015) Structural Variations and Solvent Structure of r(UGGGGU) Quadruplexes Stabilized by Sr2+ Ions. Journal of Molecular Biology 427: 2205–2219. doi:10.1016/j.jmb.2015.03.022
Garant JM, Luce MJ, Scott MS, Perreault JP, (2015) G4RNA: An RNA G-Quadruplex Database. Database 2015: 1–5. doi:10.1093/database/bav059
Gavathiotis E, Searle MS, (2003) Structure of the Parallel-Stranded DNA Quadruplex d(TTAGGGT)4 Containing the Human Telomeric Repeat: Evidence for A-Tetrad Formation from NMR and Molecular Dynamics Simulations. Organic & Biomolecular Chemistry 1: 1650–1656. doi:10.1039/b300845m
Gomez D, Guedin A, Mergny J.-L, Salles B, Riou J.-F, Teulade-Fichou M.-P, Calsou P, (2010) A G-Quadruplex Structure within the 5′-UTR of TRF2 mRNA Represses Translation in Human Cells. Nucleic Acids Research 38: 7187–7198. doi:10.1093/nar/gkq563
Gudanis D, Popenda L, Szpotkowski K, Kierzek R, Gdaniec Z, (2016) Structural Characterization of a Dimer of RNA Duplexes Composed of 8-Bromoguanosine Modified CGG Trinucleotide Repeats: A Novel Architecture of RNA Quadruplexes. Nucleic Acids Research 44: 2409-2416. doi:10.1093/nar/gkv1534
Halder K, Largy E, Benzler M, Teulade-Fichou MP, Hartig JS, (2011) Efficient Suppression of Gene Expression by Targeting 5′-UTR-Based RNA Quadruplexes with Bisquinolinium Compounds. ChemBioChem 12: 1663–1668. doi:10.1002/cbic.201100228
Huang H, Suslov NB, Li NS, Shelke SA, Evans ME, Koldobskaya Y, Rice PA, Piccirilli JA, (2014) A G-Quadruplex–containing RNA Activates Fluorescence in a GFP-like Fluorophore. Nature Chemical Biology 10: 686–691. doi:10.1038/nchembio.1561
Huppert JL, Balasubramanian S, (2005) Prevalence of Quadruplexes in the Human Genome. Nucleic Acids Research 33: 2908–2916. doi:10.1093/nar/gki609
Huppert JL, Bugaut A, Kumari S, Balasubramanian S, (2008) G-Quadruplexes: The Beginning and End of UTRs Nucleic Acids Research 36: 6260–6268. doi:10.1093/nar/gkn511
Huppert J L, (2008) Hunting G-Quadruplexes. Biochimie 90: 1140–1148. doi:10.1016/j.biochi.2008.01.014
Ji, X, Sun H, Zhou H, Xiang J, Tang Y, Zhao C, (2011) Research Progress of RNA Quadruplex. Nucleic Acid Therapeutics 21: 185–200. doi:10.1089/nat.2010.0272
Kerwin, S. (2000) G-Quadruplex DNA as a Target for Drug Design. Current Pharmaceutical Design 6: 441–471. doi:10.2174/1381612003400849
Kimura T, Xu Y, Komiyama M, (2009) Human Telomeric RNA r(UAGGGU) Sequence Forms Parallel Tetraplex Structure with U-Quartet. Nucleic Acids Symposium Series 53: 239–240. doi:10.1093/nass/nrp120
Krishnan-Ghosh Y, Stephens E, Balasubramanian S, (2004) A PNA4 Quadruplex. Journal of the American Chemical Society 126: 5944–5945. doi:10.1021/ja031508f
Kumari S, Bugaut A, Huppert JL, Balasubramanian S (2007) An RNA G-Quadruplex in the 5′ UTR of the NRAS Proto-Oncogene Modulates Translation. Nature Chemical Biology 3: 218–221. doi:10.1038/nchembio864
Laguerre A, Hukezalie K, Winckler P, Katranji F, Chanteloup G, Pirrotta M, Perrier-Cornet JM, Wong JMY, Monchaud D, (2015) Visualization of RNA-Quadruplexes in Live Cells. Journal of the American Chemical Society 137: 8521–8525. doi:10.1021/jacs.5b03413
Le, TVT, Han S, Chae J, Park HJ, (2012) G-Quadruplex Binding Ligands: From Naturally Occurring to Rationally Designed Molecules. Current Pharmaceutical Design 18: 1948–1972. doi:10.2174/138161212799958431
Lipay JM, Mihailescu MR, (2009) NMR Spectroscopy and Kinetic Studies of the Quadruplex Forming RNA r(UGGAGGU). Molecular bioSystems 5: 1347–1355. doi:10.1039/b911555b
Liu H, Matsugami A, Katahira M, Uesugi S, (2002) A Dimeric RNA Quadruplex Architecture Comprised of Two G:G(:A):G:G(:A) Hexads, G:G:G:G Tetrads and UUUU Loops. Journal of Molecular Biology 322: 955–970. doi:10.1016/S0022-2836(02)00876-8
Malgowska M, Gudanis D, Kierzek R, Wyszko E, Gabelica V, Gdaniec Z, (2014) Distinctive Structural Motifs of RNA G-Quadruplexes Composed of AGG, CGG and UGG Trinucleotide Repeats. Nucleic Acids Research 42: 10196–10207. doi:10.1093/nar/gku710
Mariani P, Spinozzi F, Federiconi F, Amenitsch H, Spindler L, Drevensek-Olenik I, (2009) Small Angle X-Ray Scattering Analysis of Deoxyguanosine 5′-monophosphate Self-Assembing in Solution: Nucleation and Growth of G-Quadruplexes. The Journal of Physical Chemistry. B 113: 7934–44. doi:10.1021/jp809734p
Mariani, P, Spinozzi F, Federiconi F, Ortore MG, Amenitsch H, Spindler L, Drevensek-Olenik I, (2010) Guanosine Quadruplexes in Solution: A Small-Angle X-Ray Scattering Analysis of Temperature Effects on Self-Assembling of Deoxyguanosine Monophosphate Journal of Nucleic Acids 2010: 1-10. doi:10.4061/2010/472478
Marquet R, Paillart JC, Skripkin E, Ehresmann C, Ehresmann B, (1994) Dimerization of Human Immunodeficiency Virus Type 1 RNA Involves Sequences Located Upstream of the Splice Donor Site Nucleic Acids Research 22: 145–151. doi:10.1093/nar/22.2.145
Martadinata H, Phan AT, (2009) Structure of Propeller-Type Parallel-Stranded RNA G-Quadruplexes, Formed by Human Telomeric RNA Sequences in K+ Solution. Journal of the American Chemical Society 131: 2570–2578. doi:10.1021/ja806592z
Martadinata H, Heddi B, Lim KW, Phan AT, (2011) Structure of Long Human Telomeric RNA (TERRA): G-Quadruplexes Formed by Four and Eight UUAGGG Repeats Are Stable Building Blocks. Biochemistry 50 (29): 6455–6461. doi:10.1021/bi200569f
Martadinata H, Phan AT, (2013) Structure of Human Telomeric RNA (TERRA): Stacking of Two G-Quadruplex Blocks in K+ Solution. Biochemistry 52: 2176–21783. doi:10.1021/bi301606u
Mashima T, Matsugami A, Nishikawa F, Nishikawa S, Katahira M, (2009) Unique Quadruplex Structure and Interaction of an RNA Aptamer against Bovine Prion Protein. Nucleic Acids Research 37: 6249–6258. doi:10.1093/nar/gkp647
Medic Š, Podbevšek P, Plavec J, (2014) Solution Structure of a Prion Protein Aptamer Analogue. Croatica Chemica Acta 87: 321–325. doi:10.5562/cca2430
Metifiot M., Amrane S, Litvak S, Andreola ML, (2014) G-Quadruplexes in Viruses: Function and Potential Therapeutic Applications. Nucleic Acids Research 42: 12352–12366. doi:10.1093/nar/gku999
Millevoi, Stefania, Hervé Moine, and Stéphan Vagner. (2012) G-Quadruplexes in RNA Biology. Wiley Interdisciplinary Reviews. RNA 3: 495–507. doi:10.1002/wrna.1113
Morris MJ, Wingate KL, Silwal J, Leeper TC, Basu S, (2012) The Porphyrin TmPyP4 Unfolds the Extremely Stable G-Quadruplex in MT3-MMP mRNA and Alleviates Its Repressive Effect to Enhance Translation in Eukaryotic Cells. Nucleic Acids Research 40: 4137–4145. doi:10.1093/nar/gkr1308
Murat P, Zhong J, Lekieffre L, Cowieson NP, Clancy JL, Preiss T, Balasubramanian S, Khanna R, Tellam J, (2014) G-Quadruplexes Regulate Epstein-Barr Virus-Encoded Nuclear Antigen 1 mRNA Translation. Nature Chemical Biology 10: 358–364. doi:10.1038/nchembio.1479
Nandakumar J, Podell ER, Cech TR, (2010) How Telomeric Protein POT1 Avoids RNA to Achieve Specificity for Single-Stranded DNA. Proceedings of the National Academy of Sciences of the United States of America 107: 651–656. doi:10.1073/pnas.0911099107
Pan B , Xiong Y, Shi K, Deng J, Sundaralingam M, (2003) Crystal Structure of an RNA Purine-Rich Tetraplex Containing Adenine Tetrads. Structure 11: 815–823. doi:10.1016/S0969-2126(03)00107-2
Pan B, Xiong Y, Shi K, Sundaralingam M, (2003a) An Eight-Stranded Helical Fragment in RNA Crystal Structure. Structure 11: 825–831. doi:10.1016/S0969-2126(03)00108-4
Pan B, Xiong Y, Shi K, Sundaralingam M, (2003b) Crystal Structure of a Bulged RNA Tetraplex at 1.1 Å Resolution. Structure 11: 1423–1430. doi:10.1016/j.str.2003.09.017
Pan B, Shi K, Sundaralingam M, (2006a) Base-Tetrad Swapping Results in Dimerization of RNA Quadruplexes: Implications for Formation of the I-Motif RNA Octaplex. Proceedings of the National Academy of Sciences of the United States of America 103: 3130–3134. doi:10.1073/pnas.0507730103
Pan B, Shi K, Sundaralingam M, (2006b) Crystal Structure of an RNA Quadruplex Containing Inosine Tetrad: Implications for the Roles of NH2 Group in Purine Tetrads. Journal of Molecular Biology 363: 451–459. doi:10.1016/j.jmb.2006.08.022
Parkinson GN, Lee MP, Neidle S, (2002) Crystal Structure of Parallel Quadruplexes from Human Telomeric DNA. Nature 417: 876–880. doi:10.1038/nature755
Randazzo A, Esposito V, Ohlenschläger O, Ramachandran R, Mayola L, (2004) NMR Solution Structure of a Parallel LNA Quadruplex. Nucleic Acids Research 32: 3083–3092. doi:10.1093/nar/gkh629
Redon S, Reichenbach P, Lingner J, (2010) The Non-Coding RNA TERRA Is a Natural Ligand and Direct Inhibitor of Human Telomerase. Nucleic Acids Research 38: 5797–5806. doi:10.1093/nar/gkq296
Russo Krauss I, Parkinson GR, Merlino A, Mattia CA, Randazzo A, Novellino E, Mazzarella L, Sica F, (2014) A Regular Thymine Tetrad and a Peculiar Supramolecular Assembly in the First Crystal Structure of an All-LNA G-Quadruplex. Acta Crystallographica. Section D, Biological Crystallography 70: 362–370. doi:10.1107/S1399004713028095
Satyanarayana M, Kim YA, Rzuczek SG, Pilch DS, Liu AA, Liu LF, Rice JE, LaVoie EJ, (2010) Macrocyclic Hexaoxazoles: Influence of Aminoalkyl Substituents on RNA and DNA G-Quadruplex Stabilization and Cytotoxicity. Bioorganic & Medicinal Chemistry Letters 20: 3150–3154. doi:10.1016/j.bmcl.2010.03.086
Schaffitzel C, Berger I, Postberg J, Hanes J, Lipps HJ, Plückthun A, (2001) In Vitro Generated Antibodies Specific for Telomeric Guanine-Quadruplex DNA React with Stylonychia Lemnae Macronuclei. Proceedings of the National Academy of Sciences of the United States of America 98: 8572–8577. doi:10.1073/pnas.141229498
Shen W, Gorelick RJ, Bambara RA, (2011) HIV-1 Nucleocapsid Protein Increases Strand Transfer Recombination by Promoting Dimeric G-Quartet Formation. Journal of Biological Chemistry 286: 29838–29847. doi:10.1074/jbc.M111.262352
Shrestha P, Shan X, Dhakal S, Tan Z, Mao H, (2014) Nascent RNA Transcripts Facilitate the Formation of G-Quadruplexes Nucleic Acids Research 42: 7236–7246. doi:10.1093/nar/gku416
Sket P, Plavec J, (2015) Diversity of DNA and RNA G-Quadruplex Structures. Future Science Chapter 2: 22–36. doi:10.4155/fseb12013.13.28.
Spindler L, Drevensek-Olenik I, Copic M, Cerar J, Skerjanc J, Mariani P, (2004) Dynamic Light Scattering and 31P NMR Study of the Self-Assembly of Deoxyguanosine 5′-monophosphate: The Effect of Added Salt. The European Physical Journal. E, Soft Matter 13: 27–33. doi:10.1140/epje/e2004-00037-0
Sundquist WI, Heaphy S, (1993) Evidence for Interstrand Quadruplex Formation in the Dimerization of Human Immunodeficiency Virus 1 Genomic RNA. Proceedings of the National Academy of Sciences 90: 3393–3397. doi:10.1073/pnas.90.8.3393
Vummidi BR, Alzeer J, Luedtke NW, (2013) Fluorescent Probes for G-Quadruplex Structures. ChemBioChem 14: 540–558. doi:10.1002/cbic.201200612
Wang Y, Patel DJ (1993) Solution Structure of the Human Telomeric Repeat d[AG3(T2AG3)3] G-Tetraplex. Structure 1: 263–282. doi:10.1016/0969-2126(93)90015-9
Warner KD, Chen MC, Song W, Strack RL, Thorn A, Jaffrey SR, Ferré-D’Amaré AR, (2014) Structural Basis for Activity of Highly Efficient RNA Mimics of Green Fluorescent Protein. Nature Structural & Molecular Biology 21: 658–663. doi:10.1038/nsmb.2865
Webba da Silva M, (2007) NMR Methods for Studying Quadruplex Nucleic Acids. Methods 43: 264–277. doi:10.1016/j.ymeth.2007.05.007
Xiong YX, Huang ZS, Tan JH, (2015) Targeting G-Quadruplex Nucleic Acids with Heterocyclic Alkaloids and Their Derivatives. European Journal of Medicinal Chemistry 97: 538–551. doi:10.1016/j.ejmech.2014.11.021
Xu S, Li Q, Xiang J, Yang Q, Sun H, Guan A, Wang L, (2015) Directly Lighting up RNA G-Quadruplexes from Test Tubes to Living Human Cells. Nucleic Acids Research 43: 9575–9586. doi:10.1093/nar/gkv1040
Xu Y, Kaminaga K, Komiyama M, (2008a) Human Telomeric RNA in G-Quadruplex Structure. Nucleic Acids Symposium Series 52: 175–176. doi:10.1093/nass/nrn089
Xu Y, Kaminaga K, Komiyama M, (2008b) G-Quadruplex Formation by Human Telomeric Repeats-Containing RNA in Na+ Solution. Journal of the American Chemical Society 130: 11179–11184. doi:10.1021/ja8031532
Xu Y, Suzuki Y, Komiyama M, (2009) Click Chemistry for the Identification of G-Quadruplex Structures: Discovery of a DNA-RNA G-Quadruplex. Angewandte Chemie 48: 3281–3284. doi:10.1002/anie.200806306
Xu Y, Ishizuka T, Kimura T, Komiyama M, (2010) A U-Tetrad Stabilizes Human Telomeric RNA G-Quadruplex Structure. Journal of the American Chemical Society 132: 7231–7233. doi:10.1021/ja909708a
Xu Y, Komiyama M, (2012) Structure, Function and Targeting of Human Telomere RNA Methods 57: 100–105. doi:10.1016/j.ymeth.2012.02.015
Zhang N, Phan AT, Patel DJ, (2005) (3 + 1) Assembly of Three Human Telomeric Repeats into an Asymmetric Dimeric G-Quadruplex. Journal of the American Chemical Society 127: 17277–17285. doi:10.1021/ja0543090
Zhang S, Wu Y, Zhang W, (2014) G-Quadruplex Structures and Their Interaction Diversity with Ligands. ChemMedChem 9: 899–911. doi:10.1002/cmdc.201300566
Acta Biochimica Polonica is an OpenAccess quarterly and publishes four issues a year. All contents are distributed under the Creative Commons Attribution-ShareAlike 4.0 International (CC BY 4.0) license. Everybody may use the content following terms: Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
Copyright for all published papers © stays with the authors.
Copyright for the journal: © Polish Biochemical Society.