RNA AND DNA EDITING -- CONTENTS -- PREFACE -- ACKNOWLEDGMENTS -- CONTRIBUTORS -- PART I DIVERSIFICATION OF THE PROTEOME THROUGH RNA AND DNA EDITING -- CHAPTER 1 DIVERSIFYING EXON CODE THROUGH A-TO-I RNA EDITING -- 1.1 Introduction and Background -- 1.1.1 Initial Discovery and Context of A-to-I RNA Editing and ADARs -- 1.1.2 Important Cases of Recoding by A-to-I Modification in Pre-mRNA -- 1.1.3 Cis-Acting Features for A-to-I Editing -- 1.1.4 Properties of the A-to-I Editing Machinery -- 1.2 Main Questions in the Field and Approaches -- 1.2.1 Biochemical Versus Computational Approaches -- 1.2.2 Editing of miRNA Sequences -- 1.3 Future Directions: Evolution of Editing Sites and Machinery -- References -- CHAPTER 2 ANTIBODY GENE DIVERSIFICATION BY AID-CATALYZED DNA EDITING -- 2.1 Introduction -- 2.2 Before AID -- 2.2.1 Without DNA (Darkness) and with DNA (Light) -- 2.2.2 Prominent Early Models for Antibody Diversification -- 2.2.3 How Protein Sequencing Technology Enabled an Understanding of Antibody Diversity -- 2.2.4 Somatic DNA Rearrangements Underpin V(D)J Joining and Create the Primary Antibody Repertoire -- 2.2.5 Additional Antibody Diversity by Somatic Hypermutation (and Gene Conversion in Some Animals) -- 2.2.6 Altering Antibody Function by Class Switch Recombination (Isotype Switching) -- 2.3 After AID -- 2.3.1 A Novel Deaminase Is Required for CSR, SHM, and IGC -- 2.3.2 AID Is a DNA Cytosine Deaminase that Directly Triggers Antibody Diversification -- 2.3.3 The Importance of Uracil Bases in DNA In Vivo -- 2.3.4 Processing of AID-induced Lesions: The Molecular Mechanism of Somatic-Hypermutation -- 2.3.5 Processing of AID-induced Lesions: The Molecular Mechanism of Immunoglobulin Gene Conversion -- 2.3.6 Processing of AID-induced Lesions: The Molecular Mechanism of Class Switch Recombination -- 2.4 Hot Areas and Speculations.

2.4.1 Immunodeficiency Syndromes Caused by Defects in AID-Mediated Ig Gene Diversification -- 2.4.2 Regulating the DNA Mutator Activity of AID -- 2.4.3 Misregulation of AID and Cancer -- 2.4.4 AID Is But One Member of a Much Larger Family of Polynucleotide Deaminases -- 2.5 Conclusions -- Acknowledgments -- References -- CHAPTER 3 PROTEIN-PROTEIN AND RNA-PROTEIN INTERACTIONS IN U-INSERTION/DELETION RNA EDITING COMPLEXES -- 3.1 A Bizarre Phenomenon and its Raison D'être -- 3.2 The Catalytic Mechanism and Machinery -- 3.3 Extent of U-Insertion/Deletion RNA Editing in Trypanosoma and Leishmania Species -- 3.4 Functional Studies of Editing Complex Subunits -- 3.4.1 REN1, REN2, and MP67. Endonuclease Homologs -- 3.4.2 REX1 and REX2. Exonuclease Homologs -- 3.4.3 RET2. TUTase -- 3.4.4 REL1 and REL2. Ligase Homologs -- 3.4.5 MP81, MP63, MP42, MP46, MP44, MP24, MP18. Structural Components -- 3.5 RNA-Protein Interactions: Isolated Subunits and Assembled Editing Complexes -- 3.5.1 MP42 -- 3.5.2 MP24 -- 3.5.3 RNA-Protein Interactions in Assembled Editing Complexes -- 3.6 Concluding Remarks -- Acknowledgments -- References -- CHAPTER 4 MACHINERY OF RNA EDITING IN PLANT ORGANELLES -- 4.1 Introduction -- 4.2 Mechanism of Target Recognition -- 4.3 PPR Protein is a Trans-Factor in Plastids -- 4.4 How Can the Model Be Generalized to Plant RNA Editing? -- 4.5 Can Closely Located Editing Sites Share a Trans-Factor? -- 4.6 Is a Trans-Factor Specific to a Single Cis-Element? -- 4.7 Mechanism Determining the Efficiency of RNA Editing -- 4.8 Co-Evolution of Trans-Factors and Editing Sites -- 4.9 What is an Editing Enzyme? -- 4.10 A Model of Editing Machinery in Plastids -- 4.11 Future Directions -- Acknowledgments -- References -- PART II FUNCTIONAL COORDINATION OF RNA EDITING WITH OTHER CELLULAR MECHANISMS -- CHAPTER 5 TRANSFER RNA EDITING ENZYMES.

AT THE CROSSROADS OF AFFINITY AND SPECIFICITY -- 5.1 Introduction: Structural Versus Functional tRNA Editing -- 5.2 Transfer RNA Editing for Structure -- 5.2.1 C-to-U Editing of the tRNA Backbone -- 5.2.2 A-to-I Editing and Modification at Position 37 and 57 of tRNAs -- 5.3 Transfer RNA Editing for Function -- 5.3.1 The Lysidine Story -- 5.3.2 Nucleotide Additions at the Ends of tRNAs -- 5.3.3 C-to-U Editing in Marsupials and Trypanosomatids -- 5.3.4 A-to-I Editing of tRNAs in Yeast and Bacteria -- 5.3.5 Double Editing in Trypanosomatids -- 5.4 The Transfer RNA Editing Enzymes of Trypanosomatids: A Special Case of Catalytic Flexibility -- 5.5 Complex Formation by Transfer RNA Editing Enzymes: A Model for the Regulation of Editing Activity -- 5.6 Concluding Remarks: Evolution of Transfer RNA Editing Deaminases: Affinity Versus Specificity -- References -- CHAPTER 6 A-TO-I EDITING AS A CO-TRANSCRIPTIONAL RNA PROCESSING EVENT -- 6.1 Introduction -- 6.1.1 Overview of Co-transcriptional Pre-mRNA Processing -- 6.1.2 Localization of the ADAR Proteins -- 6.1.3 A-to-I Editing as a Pre-mRNA Processing Event -- 6.2 Main Questions in the Field and Approaches -- 6.2.1 Why Are Edited Sites Often Situated Close to Exon/Intron Border? -- 6.2.2 The Potential of A-to-I Editing in Changing the Transcriptome -- 6.2.3 RNA Editing, the Influence on Pre-mRNA Splicing and Vice Versa -- 6.3 Can Editing Influence the Fate of a Messenger RNA in Other Ways? -- 6.3.1 Editing and Its Potential Effect on RNA Export -- 6.3.2 Editing as a Modulator of RNA Stability -- 6.3.3 Editing and Its Influence on Polyadenylation -- 6.4 Prospectives for Future Research -- References -- CHAPTER 7 STUDYING AND WORKING WITH RIBONUCLEOPROTEINS THAT CATALYZE H/ACA GUIDED RNA MODIFICATION -- 7.1 Introduction -- 7.2 Discovery of Complex (RNA-guided) Pseudouridine Synthases.

7.3 Approaches and Challenges -- 7.4 RNP Reconstitution -- 7.5 Lessons from Archaeal H/ACA RNPs -- 7.6 Biogenesis of Eukaryotic H/ACA RNPs -- 7.7 Debate on Dyskeratosis Congenita -- 7.8 Importance and Future of H/ACA RNPs -- Acknowledgments -- References -- CHAPTER 8 FUNCTIONAL ROLES OF SPLICEOSOMAL SNRNA MODIFICATIONS IN PRE-MRNA SPLICING -- 8.1 Introduction -- 8.2 Modified Nucleotides in Spliceosomal SNRNAS -- 8.3 Functional Analysis of Spliceosomal SNRNA Modifications -- 8.4 Modified Nucleotides of U2 SNRNA are Important for Pre-MRNA Splicing -- 8.5 U2 Modifications Contribute to SNRNP Biogenesis and Spliceosome Assembly -- 8.6 Genetic Analysis of U2 Modification in Yeast -- 8.7 Cytotoxicity Associated with 5FU Treatment is a Result of Inhibition on Pseudouridylation and Splicing -- 8.8 Biophysical Analysis of U2 SNRNA Modification -- 8.9 Concluding Remarks -- References -- CHAPTER 9 A ROLE FOR A-TO-I EDITING IN GENE SILENCING -- 9.1 Expression of Double-Stranded RNA in Cells -- 9.2 The Activity of ADAR in the Nucleus -- 9.3 Alternative Fates of Edited RNAs in the Nucleus -- 9.4 A Possible Connection Between RNA Editing and Gene Silencing -- 9.4.1 Heterochromatin -- 9.4.2 RNAi-Directed Heterochromatin Formation -- 9.4.3 Connections Between RNAi and dsRNA Editing -- 9.4.4 Vigilin -- 9.4.5 Recognition of RNA by Vigilins -- 9.4.6 The Vigilin Complex -- 9.5 A Model for the Nuclear Function of Vigilin -- References -- CHAPTER 10 BIOLOGICAL IMPLICATIONS AND BROADER-RANGE FUNCTIONS FOR APOBEC-1 AND APOBEC-1 COMPLEMENTATION FACTOR (ACF) -- 10.1 Overview -- 10.2 Background to Our Current Understanding of C-to-U Editing of APOB MRNA: Canonical Functions for Apobec-1 and ACF -- 10.2.1 Role of Cis-Acting Elements -- 10.2.2 Identification and Characterization of Trans-Acting Factors.

10.3 Current Understanding of Apobec-1 and ACF: Structure-Function and Genetic Regulation -- 10.3.1 Apobec-1: Structure-Function Relationships -- 10.3.2 Functions of Apobec-1 Beyond apoB mRNA Editing -- 10.3.3 Apobec-1: Genetic Regulation and Gain- and Loss-of-Function -- 10.3.4 ACF: Structure-Function Relationships -- 10.3.5 Intersections of Apobec-1 and ACF Regulation in the Modulation of C-to-U RNA Editing -- 10.4 Implications and Broad-Range Function for Apobec-1 and ACF: Future Directions and Overarching Questions -- 10.4.1 Apobec-1 -- 10.4.2 ACF -- 10.5 Conclusions -- Acknowledgments -- References -- CHAPTER 11 ANTIVIRAL FUNCTION OF APOBEC3 CYTIDINE DEAMINASES -- 11.1 Explanation of Vif Phenotype Uncovers a Unique Innate Resistance to HIV-1 Infection -- 11.2 Antiviral Functionality of the APOBEC3 Family of Proteins -- 11.2.1 Mechanism of Action -- 11.2.2 APOBEC3 Proteins and the Prevention of Zoonosis -- 11.2.3 In Vivo Correlations Between APOBEC3 Expression and Disease Course -- 11.3 The Battle for Control: Viral Suppression of the APOBEC3 Proteins -- 11.3.1 The Hijacking of the Proteasomal Degradation Pathways -- 11.3.2 Virion Exclusion of the APOBECs via a Viral-Dependent Mechanism -- 11.4 Cellular Function and Regulation of the APOBEC3 Family -- 11.4.1 Guardians of the Genome: APOBEC3-Mediated Suppression of Cellular Retroelements -- 11.4.2 Subcellular Localization (Sequestration) -- 11.4.3 Control of the Expression of the APOBEC3 Family is Exerted Transcriptionally -- 11.5 Research Questions and the Hope of Therapeutic Manipulation of the APOBEC3 Family -- 11.5.1 The "Alternative Function" -- 11.5.2 Protein Partitioning/Subcellular Localization -- 11.5.3 Protein Cofactors and Posttranslational Modifications -- 11.5.4 Therapeutic Potential -- References -- PART III PREDICTIVE STRUCTURES -- CHAPTER 12 A-TO-I EDITING OF ALU REPEATS.

12.1 Background.