Fine-Tuning of RNA Functions by Modification and Editing (Topics in Current Genetics)

1.1 Discovery of modified nucleosides......Page 1
1.2 Discovery of RNA modification enzymes......Page 3
1.3.1 Insertion/deletion of nucleotides......Page 4
1.3.2 Conversion of bases mediated by deaminases......Page 5
1.3.4 RNA editing or RNA modification?......Page 6
1.4.2 Transglycosylases......Page 7
1.4.3 Guide-RNA-mediated RNA modification machinery......Page 8
1.5 Localization and temporal order of RNA modification/editing......Page 9
2.2 Not all nucleosides in RNAs are fully modified/edited......Page 11
2.3 Fine-tuning of RNA structure and function......Page 12
3 Conclusion and further prospects: unravel biological complexity......Page 14
1.1 The wobble rule and the role of RNA modification in decoding......Page 23
1.3 Modified adenosine (inosine)......Page 26
1.4 Modified guanosines......Page 27
2.1 Non-essential RNA modifications......Page 28
2.2 Essential RNA modifications......Page 31
3.1 Identification of an essential gene responsible for lysidine formation......Page 32
3.2 In vitro lysidine synthesis by TilS......Page 34
3.3 Mechanism of lysidine synthesis......Page 35
3.4 Direct conversion of the amino acid specificity of tRNAIle due to the lysidine modification......Page 36
3.6 Recognition of tRNAIle by TilS......Page 37
3.7 Evolution of wobble modifications and genetic code assignment of AUA codon......Page 39
4.1 Post-transcriptional modifications control the subcellular localization of RNA molecules......Page 40
4.2 Role of wobble modifications in the tRNA sorting mechanism in Leishmania tarentolae......Page 41
5.1 Mitochondrial wobble modifications and the minimal decoding system......Page 43
5.2 Biosynthesis of taurinomethyluridines......Page 47
5.3 Role of mitochondrial tRNA-specific 2-thiouridylase (MTU1) in the
synthesis of τm5s2U......Page 49
5.4 Wobble modification defects in mitochondrial diseases......Page 51
5.5 Molecular pathogeneses of mitochondrial diseases......Page 53
6 RNA modification disorders as a cause of human diseases......Page 56
7.1 Amino acid conjugation involved in RNA modifications......Page 58
1 Introduction......Page 70
2 RNA modification and trans-splicing......Page 71
3 RNA editing and protein secretion......Page 75
4 Role of modifications on sub-cellular localization of tRNAs......Page 77
5 The story of tRNATrp in trypanosomatids: where editing meets modification......Page 80
6 Concluding remarks......Page 82
2 tRNA maturation......Page 86
3 Modified nucleosides in tRNA......Page 88
4 Genes required for formation of modified nucleosides in tRNA......Page 90
4.1 Pseudouridine (Ψ)......Page 91
4.3 5-methyluridine (m5U)......Page 94
4.4 5-methoxycarbonylmethyluridine (mcm5U) and 5- methoxycarbonylmethyl-2-thiouridine (mcm5s2U) In......Page 97
4.6 1-methylguanosine (m1G)......Page 98
4.8 N2,N2-dimethylguanosine ( 2 2 m G)......Page 99
4.10 N4-acetylcytidine (ac4C)......Page 100
4.13 1-methyladenosine (m1A)......Page 101
4.15 2\'-O-ribosyladenosine (phosphate) (Ar(p))......Page 102
5 Phenotypes of tRNA modification mutants......Page 103
6 Genetic approaches to study function of modified nucleosides and their modifying enzymes......Page 106
7 Concluding remarks and future prospects......Page 108
1 Introduction......Page 120
2 The m1A methyltransferases (MTases)......Page 122
3 m1A influences tRNA structure......Page 123
3.1 m1A58 and tRNA structure......Page 124
3.2 m1A9 in mitochondrial tRNA structure and function......Page 125
4 m1A58 and HIV replication......Page 127
5 m1A58 function in stabilizing tRNAi Met from S. cerevisiae......Page 128
6 Conclusions and perspectives......Page 133
1 Introduction......Page 139
2.1 The 5’-terminal cap structure......Page 140
2.2.1 Cap effects on translation......Page 141
2.2.2 Cap effects on mRNA transport......Page 142
2.2.4 Cap effects on mRNA degradation......Page 143
2.3 Enzymes involved in cap methylation......Page 144
3.1 Nucleoside modification by deamination......Page 146
3.3 N6-methyladenosine......Page 147
3.3.1 Sequence specificity of m6A in vivo......Page 148
3.3.2 Sequence specificity of m6A in vitro......Page 150
3.4.1 Mutation of m6A sites......Page 151
3.4.2 Studies utilizing methylation inhibitors......Page 153
4 Characterization and purification of HeLa mRNA N6- adenosine methyltransferase......Page 154
4.2 Further characterization of MT-B......Page 156
4.4 MT-A70 is the prototype of a previously undescribed class of putative RNA adenosine methyltransferases in a wide variety of organisms......Page 157
5 IME4 is the S. cerevisiae ortholog of MT-A70......Page 159
5.1 m6A is present in mRNA isolated from sporulating yeast......Page 161
5.2 IME4 is necessary for m6A formation in sporulating yeast......Page 162
6.1 RNA interference transfection......Page 165
6.2 Loss of MT-A70 leads to HeLa cell apoptosis......Page 166
7 Conclusion......Page 168
1 Introduction......Page 176
2.1 Transcription of snRNAs......Page 177
2.2 m7G-dependent nuclear export of UsnRNAs......Page 178
2.3 Assembly of the snRNP core structure (SMN complex) In the cytoplasm of mammalian cells, the Sm proteins assemble......Page 180
2.4 m7G-cap hypermethylation......Page 182
2.5 Nuclear import......Page 184
2.6 Sub-nuclear localization......Page 185
3.1 Three-dimensional structures of m7G-cap binding proteins......Page 187
3.2 Three-dimensional structure of the m3G-cap binding domain of human snurportin1......Page 189
4 Conclusions and outlook......Page 191
1.1 The spliceosome......Page 202
1.2 Modified bases in structural RNAs......Page 203
1.2.1 Pseudouridine ( ψ) and its features......Page 204
1.2.2 ψ residues in the spliceosome......Page 205
2.1 Structural features of the unmodified branch site helix......Page 206
2.2 Structural features of the ψ-modified branch site helix......Page 207
2.2.2 Interaction of ψ with the opposing adenosine......Page 208
3.1 Global interactions with solvent......Page 209
3.2 Local interactions with water......Page 210
4.1 Electrostatic surface features of the ψ-dependent branch site
helix......Page 211
5 Extrapolation from the branch site duplex to the native context......Page 213
7 Outlook......Page 214
1 Introduction......Page 219
2 Discovery of eukaryotic snoRNAs that guide rRNA modifications......Page 220
2.1 Early studies of snoRNAs......Page 221
2.3 Discovery that Box C/D snoRNAs guide rRNA 2\'-O-methylation......Page 222
2.5 Toward identification of complete sets of rRNA modification guide snoRNAs......Page 224
3 RNAs also guide the pseudouridylation and 2\'-Omethylation of snRNAs......Page 225
4 sno/scaRNAs may also guide mRNA modifications......Page 228
5 Small RNA–guided RNA modification of rRNA and tRNA in archaea......Page 229
6 Gene organization and biosynthesis of snoRNAs......Page 230
7 Modification guide RNAs function as RNA-protein complexes......Page 231
7.2 Protein components of pseudouridylation guide RNPs......Page 232
7.3 Evolutionary relationships between archaeal and eukaryotic modification guide RNPs......Page 233
8.1 Methylation guide RNP structure......Page 235
8.1.2 Structure of archaeal methylation guide RNPs......Page 237
8.2 Pseudouridylation guide RNP structure......Page 239
8.2.1 Structure of eukaryotic pseudouridylation guide RNPs......Page 240
8.2.2 Structure of archaeal pseudouridylation guide RNPs......Page 241
9 Function of pseudouridylation and 2\'-O-methylation......Page 242
9.2 rRNA modifications in the peptidyl transferase center contribute to ribosome function and cell growth......Page 243
9.3 Spliceosomal snRNA modifications are required for pre-mRNA splicing......Page 244
9.5 Are RNA modifications reversible?......Page 246
10 Concluding remarks......Page 247
1 Introduction......Page 259
2 Pseudouridylations conserved in bacteria and eukaryotes......Page 263
3 Base modification and their enzymes......Page 264
4 2’-O-ribose methylations conserved in bacteria and eukaryotes......Page 266
5 The outstanding case of Spb1p: an essential sitespecific enzyme in a world of snoRNA-guided modifications......Page 267
5.2.1 Mrm2p is a mitochondrial rRNA MTase......Page 268
5.2.3 Spb1p is a nucleolar site-specific rRNA MTase......Page 269
6 Perspectives: how can modifications extend the ability of RNA molecules......Page 274
1 Introduction......Page 281
2 Ribosomal RNA modifications......Page 282
3 The antibiotic resistance rRNA methyltransferases......Page 283
4 Resistance to antibiotics targeting the small subunit rRNA......Page 285
4.2 Resistance by methylation of the small subunit rRNA......Page 286
5.1 Thiopeptide antibiotics......Page 290
5.2 Orthosomycin antibiotics......Page 291
5.3 MLSB antibiotics......Page 292
5.3.2 General mechanism of MLSB resistance......Page 293
6 Synergistic effects of dual rRNA methylations......Page 294
7 Conclusion and future perspectives......Page 295
1.1 Recoding events......Page 304
1.2 The stimulatory recoding signals......Page 305
1.3 Modified nucleotides in RNA and decoding......Page 306
1.5 Testing the roles of modified nucleotides of RNA in recoding......Page 309
2.1 Programmed +1 frameshifting in bacteria......Page 311
2.2 Programmed +1 frameshifting in Eukarya......Page 313
2.3 Programmed -1 frameshifting in Bacteria and Eukarya......Page 315
3 Modified nucleotides in tRNA also affect stop codon readthrough efficiency......Page 318
4 Conclusions and Perspectives......Page 321
1 Introduction: ADAR RNA editing in vertebrates......Page 336
1.1 Functional studies on vertebrate ADAR2......Page 340
1.2 Functional studies on vertebrate ADAR1......Page 341
1.3 Other ADAR genes in vertebrates......Page 344
1.4 Searches for edited transcripts in human cells......Page 345
2 RNA editing in Drosophila......Page 346
2.1 Edited transcripts in Drosophila: from serendipity to systematic identification......Page 348
4 RNA editing in C. elegans......Page 351
Conclusion......Page 352
1 Introduction......Page 360
2 Site-specific apoB mRNA editing: the basic facts......Page 361
3 Characteristics of the RNA substrate......Page 362
4.1 Requirement of APOBEC-1 for C to U mRNA editing......Page 364
4.2 Catalytic residues, RNA binding and oligomerization of APOBEC-1......Page 365
4.3 Post-translational modification of APOBEC-1......Page 367
4.5 Comparative models of APOBEC-1 and AID......Page 368
4.6 APOBEC-1 and dC to dU DNA mutation......Page 371
4.7 APOBEC-1 and neoplasia......Page 372
5.1 Emergence of the C to U editosome concept......Page 373
5.3 APOBEC-1 complementation factor (ACF)......Page 374
5.4 Other auxiliary proteins......Page 375
6.1 APOBEC-1......Page 376
6.2 ACF......Page 377
7 Regulation of apoB mRNA editing......Page 378
8 Prospective for APOBEC-1 and APOBEC-1 related proteins......Page 380
1 Introduction......Page 396
2.1 Function of the modified nucleotides of tRNA......Page 397
2.2 Selective uptake of primer tRNA into the viral particle......Page 399
2.3 Initiation of reverse transcription......Page 400
2.3.1 The tRNA-vRNA initiation complex......Page 401
2.3.2 Anticodon modifications......Page 403
2.3.3 The tRNALys 3 core modifications......Page 404
2.4 Plus strand strong stop synthesis......Page 405
3.1.1 Permissive and non-permissive cell lines......Page 406
3.2.1 Non-random deamination of (-) strand HIV-1 DNA by APOBEC3G......Page 407
3.2.2 Consequences of HIV-1 DNA editing......Page 409
3.3.1 Vif binds APOBEC3G and prevents its incorporation into virions......Page 411
3.3.2 Vif decreases the cytoplasmic APOBEC3G concentration......Page 412
3.3.4 Editing, antiviral defences, and viral evolution......Page 413
4 Conclusions......Page 414
1 Introduction......Page 425
2 Sec tRNA[Ser]Sec......Page 426
3 Generation of mouse models......Page 427
3.1 Selective rescue of selenoprotein expression......Page 429
4 Discussion and concluding remarks......Page 430