Control of Messenger RNA Stability (eBook)

Joel G. Belasco, George Brawerman (Herausgeber)

eBook Download: PDF | EPUB

2012 | 1. Auflage
517 Seiten
Elsevier Reference Monographs (Verlag)
978-0-08-091652-1 (ISBN)

Infos

This is the first comprehensive review of mRNA stability and its implications for regulation of gene expression. Written by experts in the field, Control of Messenger RNA Stability serves both as a reference for specialists in regulation of mRNA stability and as a general introduction for a broader community of scientists. - Provides perspectives from both prokaryotic and eukaryotic systems - Offers a timely, comprehensive review of mRNA degradation, its regulation, and its significance in the control of gene expression - Discusses the mechanisms, RNA structural determinants, and cellular factors that control mRNA degradation - Evaluates experimental procedures for studying mRNA degradation

Inhalt

Front Cover 1
Control of Messenger RNA Stability 4
Copyright Page 5
Table of Contents 6
Contributors 14
Preface 18
PART I: PROKARYOTES 20
Chapter 1. mRNA Degradation in Prokaryotic Cells: An Overview 22
I. Introduction 22
II. Ribonucleases 24
III. Structural Determinants of mRNA Stability and Instability 25
IV. Mechanisms of mRNA Degradation 27
References 30
Chapter 2. The Role of the 3' End in mRNA Stability and Decay 32
I. Introduction 32
II. The 3'– 5' Exoribonucleases: PNPase and RNase II 35
III. 3' Stem–Loop Structures Stabilize Upstream mRNA 37
IV. How Do Stem–Loop Structures Stabilize Upstream mRNA? 39
V. 3' Stem–Loop Structures Influence Gene Expression 40
VI. Degradation of mRNA Stabilized by 3' Stem–Loops 42
VII. Stem–Loop-Binding Proteins 43
VIII. Chloroplasts 44
IX. Concluding Remarks: The Role of the 3' End in Regulation 45
References 46
Chapter 3. 5' mRNA Stabilizers 50
I. Introduction 50
II. Function of a 5' Stabilizer 51
III. Escherichia coli trp mRNA 56
IV. Escherichia coli ompA Message 58
V. erm Genes of Gram-Positive Bacteria 64
VI. Conclusions 68
References 69
Chapter 4. RNA Processing and Degradation by RNase K and RNase E 72
I. Introduction 72
II. Original Phenotypes of the Escherichia coli amsts and rnets Mutations 73
III. The amsts and rnets Mutations Map to the Same Gene 74
IV. The Endoribonucleases RNase K and RNase E 75
V. The ams/rne Gene Product and Its Relation to RNase K and RNase E 77
VI. ams/rne-Dependent Cleavage Sites 82
VII. Concluding Summary 85
References 86
Chapter 5. RNA Processing and Degradation by RNase III 90
I. Introduction 90
II. RNase III Enzyme and Its Substrates 90
III. rnc: The Gene for RNase III 98
IV. Regulation of rnc Expression and RNase III Activity 102
V. Ribosomal RNA Processing 104
VI. Control of Gene Expression by RNase III 106
VII. RNase III of Schizosaccharomyces pombe and Other Organisms 125
VIII. Homology between RNase III and Other Double-Strand RNA-Binding Proteins 126
References 127
Chapter 6. Translation and mRNA Stability in Bacteria: A Complex Relationship 136
I. The Relation of Translation to mRNA Stability 136
II. Effects of Interfering with Translation on mRNA Stability 138
III. The Expected Relation between Translation Frequency and mRNA Stability 142
IV. The Observed Relation between Translation Frequency and mRNA Stability 149
V. Conclusion 156
Appendix 157
References 160
PART II: EUKARYOTES 166
Chapter 7. mRNA Degradation in Eukaryotic Cells: An Overview 168
I. Importance in Control of Gene Expression 168
II. Basis for Selectivity in mRNA Degradation 169
III. Nucleases Involved in mRNA Decay, and Their Targets 172
IV. Relation of mRNA Decay to the Translation Process 175
References 178
Chapter 8. Hormonal and Developmental Regulation of mRNA Turnover 180
I. Introduction 180
II. History 181
III. Mechanistic Aspects of Regulated mRNA Turnover 188
IV. Linkage to Signal Transduction Pathways 190
V. Turnover Elements and trans-Acting Turnover Factors 196
VI. Degradation Target Sites and Nucleases 201
VII. Summary and Perspective 207
References 209
Chapter 9. Control of the Decay of Labile Protooncogene andv Cytokine mRNAs 218
I. Introduction 218
II. The Sequence Determinants Controlling ERG mRNA Decay 221
III. Mechanisms of mRNA Decay: The Importance of Protein Synthesis 226
IV. Deadenylation as the First Step in ERG mRNA Decay 228
V. The Cellular Factors That Control Rapid ERG mRNA Decay 232
VI. Conclusions 234
References 234
Chapter 10. Translationally Coupled Degradation of Tubulin mRNA 238
I. Introduction 238
II. Tubulin Synthesis Is Autoregulated 239
III. Tubulin Synthesis Is Regulated by Changes in the Stability of Cytoplasmic Tubulin mRNAs 242
IV. The Minimal Regulatory Sequence That Confers the Selective Instability of ß-Tubulin mRNA Is the First Four Translated Codons 242
V. Degradation of ß-Tubulin mRNA Is Mediated by Cotranslational Binding of a Cellular Factor to the ß-Tubulin Nascent Peptide 243
VI. What Binds to the Nascent ß-Tubulin Peptide? 248
VII. Regulation of a-Tubulin Synthesis 250
VIII. Other Mechanisms Regulating Tubulin Expression 252
IX. A Model for Cotranslational Tubulin RNA Degradation: Parallels with Other Examples of Cotranslational mRNA Decay 253
References 255
Chapter 11. Iron Regulation of Transferrin Receptor mRNA Stability 258
I. Overview of Cellular Iron Homeostasis 258
II. Iron Acquisition 259
III. Iron Sequestration 259
IV. Regulation of Cellular and Iron Homeostasis 259
V. The Iron-Responsive Element-Binding Protein as the Cellular "Ferrostat" 262
VI. The Rapid Turnover Determinant of the Transferrin Receptor mRNA 266
VII. The Structure of the TfR mRNA Regulatory Region 271
VIII. The Mechanism of TfR mRNA Decay 275
IX. Summary and Perspectives 280
References 281
Chapter 12. Degradation of a Nonpolyadenylated Messenger: Histone mRNA Decay 286
I. Introduction 286
II. Control of Histone mRNA Stability 289
III. Biochemical Mechanisms Regulating Histone mRNA Degradation 294
IV. Cell-Cycle Specific Signals and Histone mRNA Degradation 304
V. Why Degrade Histone mRNA? 305
References 306
Chapter 13. mRNA Turnover in Saccharomyces cerevisiae 310
I. Introduction 310
II. Measurement of mRNA Decay Rates in Yeast 312
III. Are Nonspecific Determinants Important Effectors of the Differences between Stable and Unstable mRNAs? 317
IV. cis-Acting Determinants of mRNA Instability 320
V. Approaches to Identifying trans-Acting Factors Involved in mRNA Decay 329
VI. Why Are Translation and Turnover Intimately Linked? 337
References 340
Chapter 14. Control of mRNA Degradation in Organelles 348
I. Introduction 348
II. Post-transcriptional Control of mRNA Accumulation 350
III. Roles of Nuclear Proteins in Organelle mRNA Stability 360
IV. Role of Translation in Organelle mRNA Stability 365
V. cis- and trans-Factors Affecting Organelle mRNA Stability 367
VI. Conclusions 378
References 379
Chapter 15. Control of Poly(A) Length 386
I. Background: Poly(A) and the Poly(A)-Binding Protein 386
II. Poly(A) Addition in the Nucleus 389
III. Cytoplasmic Poly(A) Metabolism 395
IV. Polyadenylation and Deadenylation in Gametes and Early Embryos 407
V. The Role of Poly(A) in mRNA Stability 419
VI. Concluding Comments 425
References 426
Chapter 16. mRNA Decay in Cell-Free Systems 436
I. Introduction 436
II. Rationale 436
III. Useful Approaches for Analyzing mRNA Stability in Vitro 439
IV. mRNA Decay Pathways, mRNases, and Regulatory Factors Identified in Cell-Free mRNA Decay Systems 445
V. Future Directions 459
References 463
Chapter 17. Eukaryotic Nucleases and mRNA Turnover 468
I. Introduction 468
II. Hydrolysis of mRNA Cap Structures 470
III. Exoribonucleases 474
IV. Endonucleases 479
V. mRNA Deadenylating Enzymes 482
VI. Concluding Remarks 484
References 486
PART III: METHODS OF ANALYSIS 492
Chapter 18. Experimental Approaches to the Study of mRNA Decay 494
I. Kinetics of mRNA Decay 494
II. Measurement of Decay Rates 495
III. Estimation of Changes in mRNA Stability by Comparison of Transcription Rates and Relative mRNA Levels 504
IV. Measurement of Poly(A) Sizes 505
V. Identification of Structural Elements That Affect mRNA Stability 508
References 510
Index 514

Textauszug

1

mRNA Degradation in Prokaryotic Cells: An Overview

Joel G. Belasco

I Introduction

The degradation of messenger RNA is one of the principal means by which genes are regulated in prokaryotic organisms. Remarkably, the instability of mRNA was anticipated by Jacques Monod and François Jacob before the actual discovery of mRNA. A key prediction of their operon model was that instructions for protein synthesis are conveyed from genes to ribosomes by a labile RNA transcript. As they pointed out (Jacob and Monod, 1961),

the structural message must be carried by a very short-lived intermediate both rapidly formed and rapidly destroyed during the process of information transfer. This is required by the kinetics of induction…. [T]he addition of inducer … provokes the synthesis of enzyme at maximum rate within a matter of a few minutes, while the removal of inducer … interrupts the synthesis within an equally short time. Such kinetics are incompatible with the assumption that the repressor–operator interaction controls the rate of synthesis of stable enzyme-forming templates.

This prediction was soon confirmed by the discovery of a highly labile RNA class with characteristics expected for messenger RNA (Brenner et al., 1961; Gros et al., 1961). That mRNA and its lability in vivo were discovered simultaneously was no accident; indeed, the high turnover rate of mRNA was instrumental to the detection of this class of RNAs, which comprise only 4% of the RNA in Escherichia coli.

Jacob and Monod’s crucial insight that a rapid genetic response to a changing cellular environment requires an unstable molecular messenger provides the biological imperative that explains the widespread instability of mRNA in all organisms. In the absence of regulation at the translational or post-translational level, the half-time for maximal response to an environmental stimulus that induces or represses transcription can be no shorter than the mRNA half-life, as the longevity of mRNA limits the rate at which the cellular concentration of a transcript can increase or decline to a new steady-state level. Furthermore, even under conditions of continuous gene expression, the instability of mRNA has a major impact on protein synthesis through its effect on the steady-state concentration of mRNA, which is as sensitive to the rate of mRNA degradation as it is to the rate of mRNA synthesis.

Rates of mRNA degradation can vary widely within a single cell. In E. coli, for example, half-lives of individual messages can be as short as 20–30 sec or as long as 50 min, with lifetimes typically between 2 and 4 min (Pedersen et al., 1978; Nilsson et al., 1984; Donovan and Kushner, 1986; Emory and Belasco, 1990; Baumeister et al., 1991). Marked differences in mRNA stability are commonly observed both for unrelated gene transcripts and for different translational units within a polycistronic transcript (Blundell et al., 1972; Belasco et al., 1985; Newbury et al., 1987; Båga et al., 1988).

Generally, mRNA half-lives do not exceed the cell doubling time. A longer mRNA lifetime would not significantly increase or prolong gene expression, as the effective mRNA “turnover” rate equals the rate of mRNA decay plus the rate of mRNA dilution by cell growth. Therefore, no matter how slowly a message is degraded, this effective turnover rate can be no slower than the cell growth rate. Along with the need of rapidly proliferating microorganisms to adapt swiftly to environmental changes in order to compete successfully for survival, this practical limit probably explains why mRNA half-lives typically are so much shorter in bacteria (0.5–50 min; about 3 min on average) and yeast (3–100 min; about 15 min on average) than in vertebrate cells (15 min to a few weeks; several hours on average). Consistent with this hypothesis, the longest half-life yet reported for a bacterial message (5–7 hr) was measured for hoxS mRNA in Alcaligenes eutrophus cells growing with a long doubling time of 20 hr (Oelmuller et al., 1990). An interesting exception is the hok gene transcript of plasmid Rl, which mediates killing of E. coli progeny cells that have failed to inherit the Rl plasmid. This long-lived mRNA must survive cell division in order to perform its function of plasmid maintenance, as it is selectively translated in plasmid-free segregants to produce a highly toxic protein (Gerdes et al., 1990).

The longevity of a given mRNA need not be fixed, but can vary in response to a variety of growth conditions and environmental signals. For example, excessive accumulation of OmpA protein in the outer membrane of E. coli is prevented under conditions of slow cell growth by accelerated degradation of the ompA transcript (Nilsson et al., 1984). Some Bacillus subtilis mRNAs that are synthesized primarily in vegetative cells (e.g., sdh mRNA, which encodes succinate dehydrogenase) or in cells entering stationary phase (e.g., aprE mRNA, which encodes subtilisin) are suddenly destabilized when cells are shifted to another growth stage (Melin et al., 1989; Resnekov et al., 1990). Furthermore, mRNAs that encode proteins important for nitrogen fixation (nif in Klebsiella pneumoniae) and photosynthesis (puf in Rhodobacter capsulatus), processes induced in these bacteria only when oxygen is scarce, are degraded more slowly under anaerobic conditions than in the presence of oxygen (Collins et al., 1986; Klug, 1991). Similarly, the Staphylococcus aureus ermC and ermA mRNAs, which encode resistance to erythromycin, are stabilized when expression of these genes is induced by the presence of low concentrations of erythromycin (Bechhofer and Dubnau, 1987; Sandler and Weisblum, 1988). Thus, modulation of gene expression can be achieved through changes in mRNA stability.

Despite its importance to gene expression, mRNA degradation has been the slowest of the principal gene regulatory processes in bacteria to be elucidated. Only now, 30 years after the discovery of the instability of mRNA, are we beginning to glimpse the structural determinants of mRNA stability and instability, the cellular factors that degrade mRNA, and the molecular mechanisms by which this process occurs. There are a number of explanations of why progress in understanding mRNA degradation has come later than major advances in the fields of prokaryotic transcription and translation regulation. These include the structural complexity of mRNA and the general failure of genetic selection to aid in the identification of cis- and trans-acting genetic loci that control mRNA lifetimes. Only with the advent of recombinant DNA technology has it become possible to address these questions effectively and to obtain detailed information about mRNA degradation in vivo.

II Ribonucleases

Although many different ribonucleases have been identified in E. coli, only a small number of these have been shown to participate in mRNA degradation. These include a few endonucleases (RNase E, RNase K, RNase III) and two 3′ exonucleases [RNase II and polynucleotide phosphorylase (PNPase)]. To date, no ribonuclease that removes single nucleotides sequentially from the 5′ end of RNA has been identified in any prokaryotic organism.

The cleavage-site specificity of RNases E, K, and III is as yet rather poorly defined. RNases E and K, which appear to be interrelated, preferentially cleave certain short, single-stranded AU-rich sequences that are located in an appropriate secondary/tertiary structural context (see Chapter 4). Biochemical characterization of RNases E and K, which have not yet been purified to homogeneity, is rather sparse. Most conclusions as to the importance of RNase E for mRNA degradation have relied on genetic evidence obtained by thermally inactivating this ribonuclease in E. coli strains with a temperature-sensitive mutation in the rne gene (also known as the ams gene). It now appears that cleavage by RNase E is the rate-determining step in the degradation of many E. coli mRNAs. RNase III (the product of the E. coli rnc gene), which participates in the degradation of a much more limited number of mRNAs, cleaves RNA at certain double-helical sites (see Chapter 5). Its substrates include most very long RNA duplexes that are perfectly paired and some RNA stem–loop structures. The key features of RNA hairpins cleaved by RNase III that causes them to be substrates for this enzyme remain ill-defined. In addition to their role in mRNA degradation, RNase E and RNase III also participate in the processing of stable RNAs, such as ribosomal RNA.

Exonucleases RNase II and PNPase (the products of the E. coli rnb and pnp genes) are enzymes that readily degrade RNA that is not base-paired at the 3′ end (see Chapter 2). RNA digestion by these two 3′ exonucleases is impeded when a significant 3′ stem–loop structure is encountered.

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Produkt-Details

• Erscheint lt. Verlag: 2.12.2012
• Sprache: englisch
• Themenwelt: Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie
• Themenwelt: Naturwissenschaften ► Biologie ► Mikrobiologie / Immunologie
• Themenwelt: Naturwissenschaften ► Biologie ► Zellbiologie
• Themenwelt: Technik
• ISBN-10: 0-08-091652-X / 008091652X
• ISBN-13: 978-0-08-091652-1 / 9780080916521