The full text of this article hosted at iucr.org is unavailable due to technical difficulties.

Angewandte Chemie International Edition
Review

Structure and Function of Noncanonical Nucleobases

Prof. Dr. Thomas Carell

Corresponding Author

E-mail address:thomas.carell@lmu.de

Center for Integrated Protein Science at the Department of Chemistry, Ludwig‐Maximilians‐Universität München, Butenandtstrasse 5–13, 81377 München (Germany)

Department für Chemie, Ludwig‐Maximilians Universität München, Butenandtstrasse 5–13, 81377 München (Germany)

Center for Integrated Protein Science at the Department of Chemistry, Ludwig‐Maximilians‐Universität München, Butenandtstrasse 5–13, 81377 München (Germany)
Search for more papers by this author
MChem. Caterina Brandmayr

Center for Integrated Protein Science at the Department of Chemistry, Ludwig‐Maximilians‐Universität München, Butenandtstrasse 5–13, 81377 München (Germany)

Department für Chemie, Ludwig‐Maximilians Universität München, Butenandtstrasse 5–13, 81377 München (Germany)

Search for more papers by this author
Dipl.‐Chem. Antje Hienzsch

Center for Integrated Protein Science at the Department of Chemistry, Ludwig‐Maximilians‐Universität München, Butenandtstrasse 5–13, 81377 München (Germany)

Department für Chemie, Ludwig‐Maximilians Universität München, Butenandtstrasse 5–13, 81377 München (Germany)

Search for more papers by this author
Dr. Markus Müller

Center for Integrated Protein Science at the Department of Chemistry, Ludwig‐Maximilians‐Universität München, Butenandtstrasse 5–13, 81377 München (Germany)

Department für Chemie, Ludwig‐Maximilians Universität München, Butenandtstrasse 5–13, 81377 München (Germany)

Search for more papers by this author
Dr. David Pearson

Center for Integrated Protein Science at the Department of Chemistry, Ludwig‐Maximilians‐Universität München, Butenandtstrasse 5–13, 81377 München (Germany)

Department für Chemie, Ludwig‐Maximilians Universität München, Butenandtstrasse 5–13, 81377 München (Germany)

Search for more papers by this author
Dipl.‐Chem. Veronika Reiter

Center for Integrated Protein Science at the Department of Chemistry, Ludwig‐Maximilians‐Universität München, Butenandtstrasse 5–13, 81377 München (Germany)

Department für Chemie, Ludwig‐Maximilians Universität München, Butenandtstrasse 5–13, 81377 München (Germany)

Search for more papers by this author
M. Sc. Ines Thoma

Center for Integrated Protein Science at the Department of Chemistry, Ludwig‐Maximilians‐Universität München, Butenandtstrasse 5–13, 81377 München (Germany)

Department für Chemie, Ludwig‐Maximilians Universität München, Butenandtstrasse 5–13, 81377 München (Germany)

Search for more papers by this author
M. Sc. Peter Thumbs

Center for Integrated Protein Science at the Department of Chemistry, Ludwig‐Maximilians‐Universität München, Butenandtstrasse 5–13, 81377 München (Germany)

Department für Chemie, Ludwig‐Maximilians Universität München, Butenandtstrasse 5–13, 81377 München (Germany)

Search for more papers by this author
Dipl.‐Chem. Mirko Wagner

Center for Integrated Protein Science at the Department of Chemistry, Ludwig‐Maximilians‐Universität München, Butenandtstrasse 5–13, 81377 München (Germany)

Department für Chemie, Ludwig‐Maximilians Universität München, Butenandtstrasse 5–13, 81377 München (Germany)

Search for more papers by this author
First published: 28 June 2012
Cited by: 72

Abstract

DNA and RNA contain, next to the four canonical nucleobases, a number of modified nucleosides that extend their chemical information content. RNA is particularly rich in modifications, which is obviously an adaptation to their highly complex and variable functions. In fact, the modified nucleosides and their chemical structures establish a second layer of information which is of central importance to the function of the RNA molecules. Also the chemical diversity of DNA is greater than originally thought. Next to the four canonical bases, the DNA of higher organisms contains a total of four epigenetic bases: m5dC, hm5dC, f5dC und ca5dC. While all cells of an organism contain the same genetic material, their vastly different function and properties inside complex higher organisms require the controlled silencing and activation of cell‐type specific genes. The regulation of the underlying silencing and activation process requires an additional layer of epigenetic information, which is clearly linked to increased chemical diversity. This diversity is provided by the modified non‐canonical nucleosides in both DNA and RNA.

Number of times cited: 72

  • , Ferrocenyl GNA Nucleosides: A Bridge between Organic and Organometallic Xeno‐nucleic Acids , ChemPlusChem, 83, 2, (77-86), (2018).
  • , Noncanonical RNA Nucleosides as Molecular Fossils of an Early Earth—Generation by Prebiotic Methylations and Carbamoylations, Angewandte Chemie International Edition, 57, 20, (5943-5946), (2018).
  • , , Angewandte Chemie, 130, 20, (6050-6054), (2018).
  • , Positive-sense RNA viruses reveal the complexity and dynamics of the cellular and viral epitranscriptomes during infection, Nucleic Acids Research, (2018).
  • , Wet-dry cycles enable the parallel origin of canonical and non-canonical nucleosides by continuous synthesis, Nature Communications, 9, 1, (2018).
  • , The Profile and Dynamics of RNA Modifications in Animals, ChemBioChem, 18, 11, (979-984), (2017).
  • , Base‐Modified Nucleic Acids as a Powerful Tool for Synthetic Biology and Biotechnology, Chemistry – A European Journal, 23, 40, (9560-9576), (2017).
  • , Solvatochromic Effects on the Absorption Spectrum of 2-Thiocytosine, The Journal of Physical Chemistry B, 121, 20, (5187), (2017).
  • , Evidence for a Double Well in the First Triplet Excited State of 2-Thiouracil, The Journal of Physical Chemistry B, 10.1021/acs.jpcb.7b06917, 121, 39, (9274-9280), (2017).
  • , Synthesis of RNA Containing 5‐Hydroxymethyl‐, 5‐Formyl‐, and 5‐Carboxycytidine, Chemistry – A European Journal, 23, 63, (15894-15898), (2017).
  • , Photorelaxation and Photorepair Processes in Nucleic and Amino Acid Derivatives, Molecules, 22, 12, (2203), (2017).
  • , Mechanism Underlying the Nucleobase-Distinguishing Ability of Benzopyridopyrimidine (BPP), The Journal of Physical Chemistry A, 10.1021/acs.jpca.7b08334, 121, 43, (8267-8279), (2017).
  • , Label-free, direct localization and relative quantitation of the RNA nucleobase methylations m6A, m5C, m3U, and m5U by top-down mass spectrometry, Nucleic Acids Research, 10.1093/nar/gkx470, 45, 13, (8014-8025), (2017).
  • , Self-Assembled Systems via Nucleobase Pairing, Comprehensive Supramolecular Chemistry II, 10.1016/B978-0-12-409547-2.12536-3, (191-257), (2017).
  • , Orientation-dependent FRET system reveals differences in structures and flexibilities of nicked and gapped DNA duplexes, Nucleic Acids Research, 45, 11, (e105), (2017).
  • , RNA cytosine methyltransferase Nsun3 regulates embryonic stem cell differentiation by promoting mitochondrial activity, Cellular and Molecular Life Sciences, (2017).
  • , Detection of 5-Methylcytosine in Specific Poly(A) RNAs by Bisulfite Sequencing, RNA Methylation, 10.1007/978-1-4939-6807-7_8, (107-121), (2017).
  • , An alkylating immobilization linker for immunochemical epigenetic assessment, Chemical Communications, 53, 59, (8308), (2017).
  • , Chemical and Conformational Diversity of Modified Nucleosides Affects tRNA Structure and Function, Biomolecules, 7, 1, (29), (2017).
  • , Reparameterizations of the χ Torsion and Lennard‐Jones σ Parameters Improve the Conformational Characteristics of Modified Uridines, Journal of Computational Chemistry, 37, 17, (1576-1588), (2016).
  • , , Angewandte Chemie, 128, 5, (1946-1950), (2015).
  • , 5‐Formylcytosine Could Be a Semipermanent Base in Specific Genome Sites, Angewandte Chemie International Edition, 55, 39, (11797-11800), (2016).
  • , Additive CHARMM force field for naturally occurring modified ribonucleotides, Journal of Computational Chemistry, 37, 10, (896-912), (2016).
  • , , Angewandte Chemie, 128, 39, (11974-11978), (2016).
  • , Fluorogenic Labeling of 5‐Formylpyrimidine Nucleotides in DNA and RNA, Angewandte Chemie International Edition, 55, 5, (1912-1916), (2015).
  • , Intersystem Crossing Pathways in the Noncanonical Nucleobase 2-Thiouracil: A Time-Dependent Picture, The Journal of Physical Chemistry Letters, 7, 11, (1978), (2016).
  • , Mass spectrometry of modified RNAs: recent developments, The Analyst, 141, 1, (16), (2016).
  • , Properties and reactivity of nucleic acids relevant to epigenomics, transcriptomics, and therapeutics, Chemical Society Reviews, 45, 9, (2637), (2016).
  • , Single Site Discrimination of Cytosine, 5-Methylcytosine, and 5-Hydroxymethylcytosine in Target DNA Using Anthracene-Tagged Fluorescent Probes, ACS Chemical Biology, 11, 3, (717), (2016).
  • , Flavin-Dependent Methylation of RNAs: Complex Chemistry for a Simple Modification, Journal of Molecular Biology, 10.1016/j.jmb.2016.10.031, 428, 24, (4867-4881), (2016).
  • , Structural effects of modified ribonucleotides and magnesium in transfer RNAs, Bioorganic & Medicinal Chemistry, 10.1016/j.bmc.2016.06.037, 24, 20, (4826-4834), (2016).
  • , Internal conversion and intersystem crossing pathways in UV excited, isolated uracils and their implications in prebiotic chemistry, Physical Chemistry Chemical Physics, 10.1039/C6CP01790H, 18, 30, (20168-20176), (2016).
  • , Enzymatic synthesis and reverse transcription of RNAs incorporating 2′-O-carbamoyl uridine triphosphate, Chemical Communications, 10.1039/C6CC05796A, 52, 87, (12889-12892), (2016).
  • , Ultrasensitive Direct Quantification of Nucleobase Modifications in DNA by Surface‐Enhanced Raman Scattering: The Case of Cytosine, Angewandte Chemie, 127, 46, (13854-13858), (2015).
  • , Ultrasensitive Direct Quantification of Nucleobase Modifications in DNA by Surface‐Enhanced Raman Scattering: The Case of Cytosine, Angewandte Chemie International Edition, 54, 46, (13650-13654), (2015).
  • , Non-homologous functions of the AlkB homologs, Journal of Molecular Cell Biology, 7, 6, (494), (2015).
  • , An atlas of RNA base pairs involving modified nucleobases with optimal geometries and accurate energies, Nucleic Acids Research, 43, 14, (6714), (2015).
  • , Cellular RNA is chemically modified by exposure to air pollution mixtures, Inhalation Toxicology, 27, 1, (74), (2015).
  • , The Literature of Heterocyclic Chemistry, Part XIII, 2012–2013, , 10.1016/bs.aihch.2015.04.002, (193-363), (2015).
  • , Pyrene‐Based Quantitative Detection of the 5‐Formylcytosine Loci Symmetry in the CpG Duplex Content during TET‐Dependent Demethylation, Angewandte Chemie, 126, 42, (11405-11409), (2014).
  • , Pyrene‐Based Quantitative Detection of the 5‐Formylcytosine Loci Symmetry in the CpG Duplex Content during TET‐Dependent Demethylation, Angewandte Chemie International Edition, 53, 42, (11223-11227), (2014).
  • , Functional implications of ribosomal RNA methylation in response to environmental stress, Critical Reviews in Biochemistry and Molecular Biology, 49, 1, (69), (2014).
  • , Polymerase Synthesis of Photocaged DNA Resistant against Cleavage by Restriction Endonucleases, Angewandte Chemie International Edition, 53, 26, (6734-6737), (2014).
  • , Detection of 3′-End RNA Uridylation with a Protein Nanopore, ACS Nano, 10.1021/nn4050479, 8, 2, (1364-1374), (2013).
  • , Conformational Preferences of Modified Uridines: Comparison of AMBER Derived Force Fields, Journal of Chemical Information and Modeling, 10.1021/ci400582a, 54, 4, (1129-1142), (2014).
  • , Dye label interference with RNA modification reveals 5-fluorouridine as non-covalent inhibitor, Nucleic Acids Research, 10.1093/nar/gku908, 42, 20, (12735-12745), (2014).
  • , TET enzymatic oxidation of 5-methylcytosine, 5-hydroxymethylcytosine and 5-formylcytosine, Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 764-765, (18), (2014).
  • , Dynamic RNA modifications in disease, Current Opinion in Genetics & Development, 26, (47), (2014).
  • , Polymerase Synthesis of Photocaged DNA Resistant against Cleavage by Restriction Endonucleases, Angewandte Chemie, 126, 26, (6852-6855), (2014).
  • , A chemical probe targets DNA 5-formylcytosine sites and inhibits TDG excision, polymerases bypass, and gene expression, Chem. Sci., 5, 2, (567), (2014).
  • , The Dnmt2 RNA methyltransferase homolog of Geobacter sulfurreducens specifically methylates tRNA-Glu, Nucleic Acids Research, 10.1093/nar/gku256, 42, 10, (6487-6496), (2014).
  • , The Readout of Base‐Pair Information in Adenine–Thymine α‐D‐Arabinonucleosides, Chemistry – A European Journal, 20, 47, (15473-15481), (2014).
  • , Structure of human RNA N6-methyladenine demethylase ALKBH5 provides insights into its mechanisms of nucleic acid recognition and demethylation, Nucleic Acids Research, 42, 7, (4741), (2014).
  • , Affinity of Molecular Ions for DNA Structures Is Determined by Solvent-Accessible Surface Area, The Journal of Physical Chemistry B, 10.1021/jp505107g, 118, 32, (9583-9594), (2014).
  • , Triplex-mediated analysis of cytosine methylation at CpA sites in DNA, Chem. Commun., 10.1039/C3CC45917A, 50, 5, (551-553), (2014).
  • , Thermochemistry of Uracils. Experimental and Computational Enthalpies of Formation of 5,6-Dimethyl-, 1,3,5-Trimethyl-, and 1,3,5,6-Tetramethyluracils, The Journal of Physical Chemistry A, 117, 1, (244), (2013).
  • , A Chemical Perspective on Transcriptional Fidelity: Dominant Contributions of Sugar Integrity Revealed by Unlocked Nucleic Acids, Angewandte Chemie International Edition, 52, 47, (12341-12345), (2013).
  • , The synthesis, antiviral, cytostatic and cytotoxic evaluation of a new series of acyclonucleotide analogues with a 1,2,3-triazole linker, European Journal of Medicinal Chemistry, 10.1016/j.ejmech.2013.10.057, 70, (703-722), (2013).
  • , First X-ray diffraction and quantum chemical study of proton-acceptor and proton-donor forms of 5-carboxylcytosine, the last-discovered nucleobase, Journal of Molecular Structure, 10.1016/j.molstruc.2013.07.023, 1050, (140-150), (2013).
  • , Research Methods for Detection and Quantitation of RNA Modifications, Materials and Methods, 3, (2013).
  • , Total Synthesis of the Hypermodified RNA Bases Wybutosine and Hydroxywybutosine and Their Quantification Together with Other Modified RNA Bases in Plant Materials, Chemistry – A European Journal, 19, 13, (4244-4248), (2013).
  • , On the Origin of the Canonical Nucleobases: An Assessment of Selection Pressures across Chemical and Early Biological Evolution, Israel Journal of Chemistry, 53, 6‐7, (469-483), (2013).
  • , Understanding the Molecular Basis of RNA Polymerase II Transcription, Israel Journal of Chemistry, 53, 6‐7, (442-449), (2013).
  • , A Chemical Perspective on Transcriptional Fidelity: Dominant Contributions of Sugar Integrity Revealed by Unlocked Nucleic Acids, Angewandte Chemie, 125, 47, (12567-12571), (2013).
  • , Künstliche genetische Systeme bestehend aus vergrößerten Basenpaaren, Angewandte Chemie, 125, 48, (12728), (2013).
  • , Ryoji‐Noyori‐Preis: M. Shibasaki / New Year Honours: C. V. Robinson und S. E. Gibson / Clara‐Immerwahr‐Preis: J. K. Edwards / Clemens‐Winkler‐Medaille: Otto S. Wolfbeis / Kuratorium der Volkswagenstiftung: T. Carell / AkzoNobel North America Science Award: K. Matyjaszewski, Angewandte Chemie, 125, 12, (3391-3392), (2013).
  • , Artificial Genetic Sets Composed of Size-Expanded Base Pairs, Angewandte Chemie International Edition, 52, 48, (12498), (2013).
  • , Ryoji Noyori Prize: M. Shibasaki / New Year Honours: C. V. Robinson and S. E. Gibson / Clara Immerwahr Award: J. K. Edwards / Clemens Winkler Medal: Otto S. Wolfbeis / Board of Trustees, Volkswagen Foundation: T. Carell / AkzoNobel North America Science Award: K. Matyjaszewski, Angewandte Chemie International Edition, 52, 12, (3309-3310), (2013).
  • , ChemInform Abstract: Structure and Function of Noncanonical Nucleobases, ChemInform, 43, 47, (2012).
  • , A Facile Synthesis of 5'-Fluoro-5'-deoxyacadesine (5'-F-AICAR): A Novel Non-phosphorylable AICAR Analogue, Molecules, 10.3390/molecules171113036, 17, 12, (13036-13044), (2012).
  • , The origin of efficient triplet state population in sulfur-substituted nucleobases, Nature Communications, 10.1038/ncomms13077, 7, (13077), (2016).
  • , Thermodynamic properties of water molecules in the presence of cosolute depend on DNA structure: a study using grid inhomogeneous solvation theory, Nucleic Acids Research, 10.1093/nar/gkv1133, (gkv1133), (2015).