Chemistry and Biology of Non-canonical Nucleic Acids

Naoki Sugimoto, PhD, is Professor at Konan University in Japan and Director of the Frontier Institute for Biomolecular Engineering Research. He received his PhD from Kyoto University, Japan in 1985. He has published over 500 scientific papers and books and is a member of the Editorial Board of Nucleic Acids Research and Scientific Reports. He is the First President of the Japan Society of Nucleic Acids Chemistry.

• Preface xi1 History for Canonical and Non-canonical Structures of Nucleic Acids 11.1 Introduction 11.2 History of Duplex 11.3 Non-Watson–Crick Base Pair 51.4 Nucleic Acid Structures Including Non-Watson–Crick Base Pairs 71.5 Perspective of the Research for Non-canonical Nucleic Acid Structures 81.6 Conclusion and Perspective 9References 92 Structures of Nucleic Acids Now 112.1 Introduction 112.2 Unusual Base Pairs in a Duplex 112.2.1 Hoogsteen Base Pair 132.2.2 Purine–Pyrimidine Mismatches 132.2.3 Purine–Purine Mismatches 142.2.4 Pyrimidine–Pyrimidine Mismatches 162.3 Non-canonical Backbone Shapes in DNA Duplex 172.4 Branched DNA with Junction 192.5 Multi-stranded DNA Helices 202.6 Structures in RNA 202.6.1 Basic Structure Distinctions of RNA 202.6.2 Elements in RNA Secondary Structures 212.6.2.1 Hairpin Loop 222.6.2.2 Bulge Loop 222.6.2.3 Internal Loop 232.6.3 Elements in Tertiary Interactions of RNA 242.6.3.1 A-Minor Interactions 252.6.3.2 Ribose Zipper 252.6.3.3 T-Loop Motif 262.6.3.4 Kissing-Loop Interaction 262.6.3.5 GNRA Tetraloop Receptor Interaction 272.6.3.6 Pseudoknot Crosslinking Distant Stem Regions 292.7 Conclusion 29References 303 Stability of Non-canonical Nucleic Acids 333.1 Introduction 333.2 Factors Influencing Stabilities of the Canonical Duplexes 343.2.1 Hydrogen Bond Formations 343.2.2 Stacking Interactions 353.2.3 Conformational Entropy 353.3 Thermodynamic Analysis for the Formation of Duplex 363.4 Factors Influencing Stabilities of the Non-canonical Nucleic Acids 393.4.1 Factors Influencing Stability of Triplexes 393.4.2 Factors Influencing Stability of Quadruplex 423.4.2.1 G-Quadruplexes 423.4.2.2 i-Motif 443.5 Thermodynamic Analysis for the Non-canonical Nucleic Acids 453.5.1 Thermodynamic Analysis for the Intramolecular Triplex and Tetraplex 453.5.2 Thermodynamic Analysis for the Intermolecular Triplex 453.5.3 Thermodynamic Analysis for the Tetraplex 463.6 Conclusion 48References 494 Physicochemical Properties of Non-canonical Nucleic Acids 514.1 Introduction 514.2 Spectroscopic Properties of Non-canonical Nucleic Acids 514.2.1 Effect of Non-canonical Structure on UV Absorption 514.2.2 Circular Dichroism of Non-canonical Nucleic Acids 534.2.3 NMR Spectroscopy 564.2.4 Other Spectroscopic Characteristics of Non-canonical Nucleic Acids 574.3 Chemical Interactions on Non-canonical Nucleic Acids 594.3.1 Hydration 594.3.2 Cation Binding 614.3.3 pH Effect 624.3.4 Chemical Modification 634.4 Chemical Platform on the Non-canonical Structures 644.4.1 Specificity of a Ligand to Non-canonical Structures 644.4.2 Fluorescence Platform of Non-canonical Structures 674.4.3 Interface Between Proteins and Nucleic Acids 684.5 Physicochemical Property of Non-canonical Nucleic Acids in Cell 694.5.1 Molecular Crowding Condition that Reflects Cellular Environments 694.5.2 Effects of Crowding Reagents on Non-canonical Nucleic Acid Structures 704.5.3 Quantification of Physical Properties of Non-canonical Structures in Crowding Condition 714.5.4 Non-canonical Structures Under Mimicking Organelle Environment 724.5.5 Insight for the Formation of Non-canonical Nucleic Acids in Cells 734.6 Conclusion 75References 755 Telomere 795.1 Introduction 795.2 Structural Properties of Telomere 795.2.1 Structures of Telomere 795.2.2 Structural Properties of Human Telomeric G4s 815.2.3 Structure of Repeats of Human Telomeric G4s 845.3 Biological Relevance of Telomere G4 865.3.1 Telomerase Activity 865.3.2 Telomerase Repeated Amplification Protocol (TRAP) Assay 895.3.3 Alternative Lengthening of Telomere (ALT) Mechanism 895.4 Other Non-canonical Structures Related to Telomere Region 895.4.1 Telomere i-Motif 895.4.2 Telomere RNA 905.5 Conclusion 92References 936 Transcription 956.1 Introduction 956.2 Transcription Process 966.2.1 Transcription Initiation 966.2.2 Transcription Elongation 986.2.3 Transcription Termination 996.3 Transcription Process Perturbed by Certain Sequences of DNA and RNA 1016.4 Transcription Process Perturbed by Non-canonical Structures of DNA and RNA 1036.5 Conclusion 110References 1107 Translation 1137.1 Introduction 1137.2 RNAs Involved in Translation Machinery 1137.3 General Process of Translation 1177.3.1 Translation Initiation 1177.3.2 Translation Elongation 1197.3.3 Translation Termination 1197.4 RNA Structures Affecting Translation Reaction 1217.4.1 Modulation of Translation Initiation in Prokaryotes 1217.4.2 Modulation of Translation Initiation in Eukaryotes 1237.4.3 RNA Structures Affecting Translation Elongation 1267.4.4 RNA Structures Affecting Translation Termination 1307.5 Conclusion 133References 1348 Replication 1378.1 Introduction 1378.2 Replication Machineries 1378.3 Replication Initiation 1388.3.1 Mechanism of Activation of Replication Origins 1388.3.2 Activation Control of Origins by G4s 1398.3.3 Control of Timing of Replication Initiation by G4s 1428.4 DNA Strand Elongation 1428.4.1 Mechanism of DNA Strand Elongation 1428.4.2 Impact of G4 and i-Motif Formations on DNA Strand Synthesis 1448.4.3 Relationship Between G4 and Epigenetic Modification 1458.4.4 Expansion and Contraction of Replicating Strand Induced by Hairpin Structures 1478.5 Termination of Replication 1488.6 Chemistry of the Replication and Its Regulation 1488.6.1 Cellular Environments 1488.6.2 Control of Replication by Chemical Compounds 1508.7 Conclusion 151References 1529 Helicase 1559.1 Introduction 1559.2 Function and Structure of Helicases 1559.3 Unwinding of Non-canonical DNA Structures by Helicases 1589.4 G4 Helicases in Gene Expressions 1629.5 G4 Helicases in Replication 1639.6 G4 Helicases in Telomere Maintenance 1649.7 Relation to Diseases by Loss of G4 Helicases 1659.8 Insight into Specific Properties of Activities of G4 Helicase Under Cellular Conditions 1659.9 Conclusion 167References 16710 Dynamic Regulation of Biosystems by Nucleic Acids with Non-canonical Structures 17110.1 Introduction 17110.2 Time Scale of Biological Reactions 17110.2.1 Cell Cycle 17210.2.2 Central Dogma 17210.2.3 Dynamic Structures of Nucleic Acids 17410.3 Processes in the Central Dogma Affected by Dynamics of Nucleic Acid Structures 17610.3.1 Epigenetic Regulation Caused by Chemical Modification of DNA 17610.3.2 Co-transcriptional Formation of Metastable RNA Structures 17810.3.3 Co-transcriptional Translation and Transcription Attenuation 18010.3.4 Co-transcriptional Ligand Binding and Gene Regulation 18110.3.5 Translation Elongation and Co-translational Protein Folding 18310.4 Conclusion 184References 18511 Cancer and Nucleic Acid Structures 18911.1 Introduction 18911.2 Detail Mechanism of Cancer 18911.2.1 Cancer Incidence 18911.2.2 The Relationship Between Genes and Cancer 19211.3 Non-canonical Structures of Nucleic Acids in Cancer Cells 19211.3.1 Structural Characteristics of Nucleic Acids in Cancer Cells 19211.3.2 Non-canonical Structures Perturb Gene Expression of Cancer-Related Genes 19511.4 Roles of Non-canonical Structures of Nucleic Acids in Cancer Cells 19711.4.1 Monitoring of Non-canonical Structures in Cancer Cells 19711.4.2 Regulation of Gene Expressions by the Non-canonical Structures in Cancer Cells 19811.5 Conclusion 199References 19912 Neurodegenerative Diseases and Nucleic Acid Structures 20312.1 Introduction 20312.2 Protein Aggregation-Induced Neurodegenerative Diseases 20312.3 DNA Shows Key Role for Neurodegenerative Diseases 20512.4 RNA Toxic Plays a Key Role for Neurological Diseases 21012.5 Conclusion 212References 21213 Therapeutic Applications 21513.1 Introduction 21513.2 Oligonucleotide Therapeutics 21613.2.1 Antisense Oligonucleotide 21613.2.2 Functions of Antisense Oligonucleotide Therapeutics 21713.2.3 Chemical Modifications in Therapeutic Oligonucleotides 22013.2.3.1 Backbone Modified Oligonucleotides 22013.2.3.2 Ribose Modified Oligonucleotides 22113.2.3.3 Oligonucleotides with Unnatural Backbone 22113.2.4 Oligonucleotide Therapeutics Other Than Antisense Oligonucleotide 22313.2.4.1 Oligonucleotide Therapeutics Functioning Through RNA Interference 22413.2.4.2 Oligonucleotide Therapeutics Functioning Through Binding to Protein 22413.3 Non-canonical Nucleic Acid Structures as Therapeutic Targets 22413.3.1 Traditional Antibiotics Targeting Structured Region of RNAs 22513.3.2 Strategies for Constructing Therapeutic Materials Targeting Structured Nucleic Acids 22613.4 Non-canonical Nucleic Acid Materials for Inducing Non-canonical Structures 23013.5 Conclusion 231References 23214 Materials Science and Nanotechnology of Nucleic Acids 23514.1 Introduction 23514.2 Non-canonical Structure-Based Nanomaterials Resembling Protein Functions 23514.2.1 Aptamer 23514.2.2 DNAzyme 23814.2.3 Ion Channel 24014.3 Protein Engineering Using G4-Binding Protein 24014.4 Regulation of Gene Expression by G4-Inducing Materials 24214.5 Environmental Sensing 24614.5.1 Sensing Temperature in Cells 24614.5.2 Sensing pH in Cells 24814.5.3 Sensing K+ Ion in Cells 24814.5.4 Sensing Crowding Condition in Cells 24914.6 Conclusion 250References 25015 Future Outlook for Chemistry and Biology of Non-canonical Nucleic Acids 25315.1 Introduction 25315.2 Exploring Potential: Properties of Non-canonical Structures in Unusual Media 25315.3 Systemizing Properties: Prediction of the Formation of Non-canonical Nucleic Acids Structures 25915.4 Advancing Technology: Applications of Non-canonical Structures Taking Concurrent Reactions into Account 26215.4.1 Co-transcriptional Dynamics of G-Quadruplex 26315.4.2 Co-transcriptional Functionalization of Riboswitch-Like Sensor 26315.4.3 Co-transcriptional RNA Capturing for Selection of Functional RNAs 26615.5 Conclusion 267References 268Index 271