Main description:

Among all cellular RNA species of the three main types, ribosomal RNA, transfer RNA or messenger RNA, be they from prokaryotic or eukaryotic organisms, the prokaryotic mRNA is unique in that it has no precursor and is synthesized in the same mature form as it is translated into proteins. In fact, ribosomes join the nascent mRNA chain and engage in protein synthesis long before its transcription is complete. Provisions are even made for slowing down the ribo somes at some sites to prevent them from catching up with the RNA-polymerase. Of course, such a situation is only possible in the prokaryotic world where there is no such thing as a nuclear mem brane physically secluding the transcription process from the cy toplasm where translation is restricted. Quite in the opposite extreme, the eukaryotic pre-messenger RNA has to suffer many and sometimes drastic steps of maturation (capping, polyadenylation, splicing, edition) before the decision is made to export it to the cytoplasm. That is where it enters the scope of this book. Once in the cytoplasm, many options are still open to it: its entrance into polysomes may be delayed (as it is in unfertilized eggs) or merely prohibited (ferritin mRNA in iron-starved cells), directed to specific locations within the cytoplasm or be more or less rapidly degraded. During gametogenesis and early development, translational control is probably the most significant level of gene expression.

Contents:

TOP Genes: A Translationally Controlled Class of Genes Including Those Coding for Ribosomal Proteins.- 1 Introduction.- 2 TOP Genes and TOP mRNAs.- 2.1 How Many TOP Genes?.- 2.2 How Much TOP mRNA?.- 3 Phenomenology of the Translational Regulation of TOP mRNAs.- 3.1 General and Specific Regulation of Protein Synthesis.- 3.2 Translational Regulation of TOP mRNAs.- 4 Some Features of TOP mRNA and of Its Translational Regulation.- 4.1 TOP mRNAs Are Capped.- 4.2 TOP mRNAs Extracted from Inactive mRNPs Are Translatable.- 4.3 Bimodal Distribution of TOP mRNA.- 4.4 Quantitative Differences in Polysome Association of Different TOP mRNAs.- 4.5 Relocation of TOP mRNA Between Polysomes and mRNPs Is Reversible and Fast.- 5 Mechanism of Translational Regulation of TOP mRNAs.- 5.1 Translational Regulation of TOP mRNA Does Not Involve a Feedback Inhibition by the Translation Product.- 5.2 Effect of the Amount of Ribosomes on TOP mRNA Translation.- 5.3 The 5UTR is the cis -Acting Element of the Translational Control.- 5.4 Some Proteins Interact with the 5'UTR of TOP mRNAs.- 5.5 Translational Regulation of TOP mRNA is Not Due to Limiting Amounts of eIF-4E.- 5.6 Effect of the Phosphorylation State of Ribosomal Protein S6 on Translational Regulation of TOP mRNA.- 5.7 Global vs. TOP mRNA Translational Regulation.- References.- RNase L: Effector Nuclease of an Activatable RNA Degradation System in Mammals.- 1 Introduction.- 2 The Interferons.- 3 The 2-5A Pathway.- 3.1 The 2-5A Synthetases.- 3.2 2-5A.- 4 RNase L.- 4.1 Detection of RNase L.- 4.2 Subcellular Localization of RNase L.- 4.3 Structure of RNase L.- 4.4 RNase L Activity.- 5 RLI.- 6 Conclusion.- References.- 3 Untranslated Regions of c-myc and c-fos mRNAs: Multifunctional Elements Regulating mRNA Translation, Degradation and Subcellular Localization.- 1 c-fos and c-myc mRNA Degradation and Translation.- 1.1 3UTR and mRNA Decay.- 1.2 3UTR and mRNA Translation.- 1.3 Is There a Link Between Translation and 3UTR-Directed Degradation?.- 2 Localization of mRNAs in the Cytoplasm and Their Association with the Cytoskeleton.- 2.1 Localization of mRNAs.- 2.2 Association of mRNAs and Polysomes with the Cytoskeleton: Cytoskeletal-Bound Polysomes.- 2.3 Cytoskeletal-Bound Polysomes Are Enriched in Specific mRNAs Including c-myc and c-fos.- 2.4 Targeting of c-myc to the Cytoskeletal and the Perinuclear Cytoplasm: Role of the 3'UTR.- 2.5 Localization Signals in c-myc mRNA.- 3 Summary and Future Perspectives.- References.- Cell-Free Systems for Analysis of Cytoplasmic mRNA Turnover.- 1 Introduction.- 2 mRNA Decay in Lower Eukaryotes.- 2.1 Tetrahymena thermophila.- 2.2 Yeast.- 3 Viral Induction of mRNA Decay.- 3.1 Herpes simplex Virus Type 1 (HSV-1).- 3.2 Human Papillomavirus Type 16 (HPV-16).- 4 mRNA Stability in Plants.- 4.1 Spinach Chloroplasts.- 4.2 Soybean.- 5 Xenopus.- 5.1 Albumin mRNA Decay in Xenopus Liver.- 5.2 Xenopus Oocyte mRNAs.- 5.2.1 Maternal mRNA Deadenylation.- 5.2.2 Maternal Xlhboxl mRNA Degradation.- 6 Chicken.- 7 Mammalian mRNA Turnover.- 7.1 Development of Functional In Vitro Decay Systems.- 7.2 Characterization of Decay Pathways.- 7.2.1 H4 Histone mRNA Decay.- 7.2.2 c-myc mRNA Decay.- 7.3 Identification/Purification of mRNases.- 7.3.1 Histone mRNA 3=>5 Exoribonuclease.- 7.3.2 Poly(A) Exoribonuclease from HeLa Cells.- 7.3.3 5=>3 Exoribonuclease in Mouse Sarcoma Ascites Cells.- 7.3.4 RNase L.- 7.4 Identification/Purification of trans-Acting Decay Regulators.- 7.4.1 c-myc mRNA Decay.- 7.4.2 Poly(A)-Binding Protein (PAB) and mRNA Stability.- 7.4.3 GM-CSF mRNA Turnover.- 7.4.4 ss -Globin mRNA Stability.- 7.5 Identification/Function of cis -Acting Instability Determinants.- 7.5.1 Insulin-Like Growth Factor I (IGF-I) mRNAs.- 7.5.2 A+ U-Rich Sequences.- 7.5.3 c-myc 3UTR and Coding Region.- 7.5.4 Ribonucleotide Reductase R2 mRNA 3UTR.- 7.6 Regulation of mRNA Decay.- 7.6.1 Histone Autoregulation.- 7.6.2 Stability of Urokinase-Type Plasminogen Activator (uPA) mRNA.- 7.6.3 Decay of Manganese Superoxide Dismutase (MnSOD) mRNAs.- 7.6.4 Stabilization of Transforming Growth Factor ssl (TGF-ssl) mRNAs.- 8 Conclusion.- References.- Mechanisms for Posttranscriptional Regulation by Iron-Responsive Elements and Iron Regulatory Proteins.- 1 Introduction.- 2 The Iron-Responsive Element (IRE): A Cis -Regulatory RNA Element.- 3 Iron-Regulatory Proteins (IRPs).- 4 Translational Control of IRE Containing RNAs by IRE/IRP Interactions in the 5UTR.- 5 Control of Transferrin Receptor mRNA Stability by IRE/IRP Interactions in the 3UTR.- 6 "Iron-Responsive" Elements Also Respond to Other Cellular Signals.- 7 Summary and Perspectives.- References.- Interaction Between Iron-Regulatory Proteins and Their RNA Target Sequences, Iron-Responsive Elements.- 1 Introduction.- 2 Biochemistry of IRP-1.- 2.1 Modulation of IRP-1 Binding Activity.- 2.2 RNA-Binding Domain of IRP-1.- 3 Evidence for a Second IRE-Binding Protein.- 4 Characterisation of IRP-2.- 4.1 Differential Iron Regulation of IRP-1 and IRP-2.- 5 Sequence and Structure of Iron-Responsive Elements.- 6 Role of IRE Loop Structure in Protein Recognition...- 7 IRP-1 and IRP-2 Bind Distinct Sets of RNA Targets.- 8 Summary.- References.- Cytoplasmic Fate of Eukaryotic mRNA: Identification and Characterization of AU-Binding Proteins.- 1 Introduction.- 2 Stable mRNAs.- 3 Unstable mRNAs.- 4 Cis -Acting Elements.- 4.1 ARE Sequence Requirements.- 4.2 Genomic Rearrangements of the ARE.- 4.3 Other Sequences.- 5 Translational Dependence of ARE-mediated mRNA Turnover.- 6 Poly(A) Shortening in ARE mRNA Decay.- 7 Subcellular Localization of mRNA Decay.- 8 How Might the ARE Be Recognized?.- 8.1 Primary Structure.- 8.2 Secondary Structure.- 9 Trans -Acting Factors.- 9.1 AUBF.- 9.2 p32 and hnRNP AO.- 9.3 hnRNPs.- 9.4 AUF-1.- 9.5 AU-A, AU-B, and AU-C.- 9.6 AU-H.- 9.7 Hel-Nl.- 10 Functions.- 11 Posttranslational Modifications.- 11.1 Phosphorylation.- 11.2 Metal Ions.- 11.3 Methylation.- 11.4 Redox State.- 12 Purification.- 13 Cloning.- 14 Sequence Information.- 15 ARE-Mediated Decay Model.- References.- Translational Control by Polyadenylation During Early Development.- 1 Introduction.- 2 Biological Importance of Translational Control in Development.- 3 Translational Repression in Oocytes.- 4 Control of Polyadenylation During Oocyte Maturation.- 4.1 Cytoplasmic Polyadenylation: Identification of Cis Elements.- 4.2 Identification of Proteins Involved in Cytoplasmic Polyadenylation.- 4.3 Deadenylation in Maturing Oocytes.- 5 Control of Polyadenylation in Eggs and Embryos.- 5.1 Polyadenylation in Embryos.- 5.2 Embryo-Specific Deadenylation.- 6 Conclusion.- References.- Function and Characterization of Poly(A)-Specific 3 Exoribonucleases.- 1 Introduction.- 2 Biochemistry of mRNA Polyadenylation.- 2.1 Polyadenylation in Mammalian Cells.- 2.1.1 Nuclear Polyadenylation.- 2.1.2 Cytoplasmic Polyadenylation.- 2.2 Polyadenylation in Yeast.- 3 The Functional Importance of RNA Poly(A) Tails ...- 3.1 Poly (A) Tail Shortening and RNA Decay.- 3.2 The Involvement of mRNA Poly(A) Tails During Translation.- 4 Poly(A)-Specific 3 Exoribonucleases.- 4.1 Mammalian Nucleases.- 4.2 Plant Nucleases.- 4.3 Trypanosomatid Nucleases.- 4.4 Yeast Nucleases.- 4.5 Bacterial Nucleases.- 5 Regulation of Poly (A) Tail Shortening.- 6 Summary and Perspectives.- References.