RNA Damage and Repair

Description

Ribonucleic acid (RNA) is a macromolecule that plays a central role in cell physiology: RNA molecules act as intermediates between the deoxyribonucleic acid (DNA), where genetic information is stored, and proteins, which perform the necessary functions within the cell. Traditionally, the structural and functional properties of RNA are closely linked to gene expression. However, RNA-based enzymes, called ribozymes, are also involved in catalysis and small RNAs regulate key cellular processes, such as cell growth, division, differentiation, aging and death. RNA is a sensitive macromolecule that can be easily damaged by environmental conditions (ultraviolet radiation, oxidative stress) and biological factors (ribonucleases, ribotoxins, CRISPR-Cas systems). Therefore, cells have developed mechanisms to protect and/or repair RNA molecules. This book presents an overview of the biology of RNA damage, protection and repair in prokaryotes and eukaryotes. Individual chapters cover the expression regulation, enzymology and physiological role of such systems, and link them to important human diseases such as cancer and degenerative diseases. Preface Contents Part I: RNA Damage and Repair in Prokaryotes Endoribonucleases of the Toxin-Antitoxin Systems Induce Abortive Infection 1 Introduction 1.1 The Arms Race Between Bacteria and Phages 1.2 The Abortive Infection (Abi) System 1.3 The Toxin-Antitoxin (TA) System 2 Functions, Structures, and Regulation of the MazF Endoribonuclease 2.1 The Abortive Infection Induced by the MazF Endoribonuclease 2.2 Phage Mechanism to Overcome MazF-Induced Abi 3 Functions, Structures, and Regulation of RnlA Endoribonuclease 3.1 The Abortive Infection Induced by RnlA Endoribonuclease 3.2 Phage Mechanisms to Overcome RnlA-Induced Abi 4 Functions, Structures, and Regulations of ToxN Endoribonuclease 4.1 The Abortive Infection Induced by ToxN Endoribonuclease 4.2 Phage Mechanisms to Overcome ToxN-Induced Abi 5 Conclusion References The Lifecycle of Ribosomal RNA in Bacteria 1 Introduction 2 Localisation and Copy Number of rDNA Operons in Bacteria 3 Organisation of rDNA Operons in Bacteria 4 Transcription Regulation of rDNA Genes Along the Microbial Growth Curve 4.1 Ribosomal DNA Promoters and Cis-Regulatory Elements 4.2 Trans-regulatory Elements 4.2.1 Regulation by Transcription Factors 4.2.2 Regulation by NTP and (p)ppGpp 5 Processing of Premature rRNA into Functional rRNAs 5.1 Maturation of 23S rRNA in E. coli 5.2 Maturation of 16S rRNA in E. coli 5.3 Maturation of 5S rRNA in E. coli 6 Bacterial rRNA Fragmentation 7 Chemical Modification of rRNA Molecules 8 Assembly of rRNAs into Ribosomes 9 rRNA Quality Control 10 Damage and Repair of Bacterial rRNA 11 Conclusion References The Rtc RNA End Healing and Sealing System 1 Introduction 2 Biological RNA Damage 2.1 CRISPR-Cas Systems 3 RNA Repair 4 The RtcA and RtcB Enzymes 4.1 The RtcA RNA Cyclase 4.2 The RtcB RNA Ligase 4.3 The RtcB RNA Ligase in Prokaryotes 4.4 The RtcB RNA Ligase in Metazoans 5 The Bacterial Rtc RNA Repair System 5.1 Diversity of the rtc Operon in Bacteria 5.2 The RtcR Transcriptional Regulator and Its CARF Domain 5.3 Expression and Function of the Rtc System in Bacteria 6 Conclusions References Part II: RNA Damage and Repair in Eukaryotes Oxidative and Nitrative RNA Modifications in Plants 1 Introduction 2 Oxidative Modifications of RNA in Plants 3 Nitrative Modifications of RNA in Plants 4 Conclusions References The Role of Ribonucleases in RNA Damage, Inactivation and Degradation 1 Introduction 2 Quality Control Mechanisms to Manage Damaged RNA 3 Ribosome Quality Control (RQC) and No-Go-Decay (NGD) 4 Xrn1, a 5′-3′ Exoribonuclease, and the Exosome, a 3′-5′ Exoribonuclease Complex 5 Cue2 as a Potential NGD Endonuclease 6 The Role of Ribonucleases in Targeting and Inactivating Host and Foreign RNA 7 Regulatory RNase 1 (Regnase-1) 8 NEDD4-Binding Protein 1 (N4BP1) 9 Zinc Finger Antiviral Protein (ZAP) and Co-Factor Nucleases 10 ZAP and KHNYN 11 ZAP and the Exosome Complex 12 The 2′,5′-Oligoadenylate Synthetase (OAS)/RNAse L System 13 Conclusion References Cytoplasmic mRNA Recapping: An Unexpected Form of RNA Repair 1 The Nature of the Cap and Its Role in mRNA Metabolism 2 Decapping and 5′ Decay 3 Early Evidence for Uncapped and Recapped Transcripts 4 The Discovery of Cytoplasmic Capping 5 The Proteins of the Cytoplasmic Capping Complex 6 Cap Homeostasis as an RNA Repair Mechanism That Modulates Translation, mRNA Decay, and Translational Control 7 Is There a Relationship Between Recapped Ends and CAGE Tags? 8 Does Cytoplasmic Capping Impact the Proteome? 9 Conclusion and Future Questions References Part III: RNA Damage in Human Diseases Adenosine-to-Inosine RNA Editing: A Key RNA Processing Step Rewriting Transcriptome in Normal Physiology and Diseases 1 Regulatory Mechanisms of A-to-I RNA Editing 1.1 Editing Regulation by Altering ADAR Expression and Activity 1.2 Editing Regulation by Affecting Subcellular Localization of ADAR 1.3 Additional Layers of A-to-I RNA Editing Regulation 2 Cross Talk of RNA Editing with Other RNA Processing and Cellular Pathways 2.1 Roles of ADARs and RNA Editing in miRNA Targeting and Biogenesis 2.2 ADARs and Splicing Regulation 2.3 ADAR Directly Promotes Proximal Polyadenylation Site 2.4 ADAR and N6-Methyladenosine 2.5 ADAR and Apoptosis 2.6 ADAR and Innate Immunity 2.7 ADAR2 and Circadian Rhythm References RNA-Mediated Metabolic Defects in Microsatellite Expansion Diseases 1 Overview of Microsatellite Expansion Diseases 2 RNA Structure and RNA-Mediated Toxicity 3 Repeat Associated Non-AUG Translation 4 Emerging Pathological Roles of microRNA 5 Defects in Nucleocytoplasmic Transport 6 Liquid-Liquid Phase Separation (LLPS) and Stress Granules 7 Conclusions and Future Perspectives References