miRNA Regulation of the Translational Machinery (eBook)

Preface 6
Contents 8
Contributors 9
Understanding How miRNAs Post- Transcriptionally Regulate Gene Expression 11
1.1 Introduction 12
1.2 miRNA Biogenesis 15
1.3 miRNA-Mediated Regulation of Eukaryotic Gene Expression 17
1.4 Summary 25
References 25
Translational Control of Endogenous MicroRNA Target Genes in C. elegans 31
2.1 Introduction 32
2.2 lin-4 and let-7 miRNAs in C. elegans Development 32
2.3 Polysome Profiling as an Assay to Assess the Translational State of mRNAs 34
2.4 MicroRNA-Mediated Gene Regulation in C. elegans: The Early View 35
2.5 MicroRNA Mediated Gene Regulation in Other Model Organisms 36
2.6 The let-7 miRNA Extensively Interacts with Translation Factors 40
2.7 Polysome Profiling Confirms Translational Repression at the Initiation Step in C. elegans 41
2.8 Inhibition of Translation Initiation and Transcript Degradation Both Depend on the GW182 Proteins AIN-1 and AIN- 2 44
2.9 Conclusions and Future Perspectives 46
References 47
Translational Inhibition by MicroRNAs in Plants 51
3.1 Introduction 52
3.2 miRNA and siRNA Biogenesis 52
3.3 ARGONAUTE Proteins 54
3.4 Translational Inhibition by Small RNAs is Common in Plants 55
3.5 Roles of miRNA-Mediated Translational Inhibition in Plants 58
3.6 Conclusion 62
References 63
Regulation of p27kip1 mRNA Expression by MicroRNAs 68
4.1 Introduction 68
4.2 miRNAs in Cancer 69
4.3 Role of p27 in Tumor Progression 71
4.4 Regulation of p27 Expression: Role of miRNAs 72
4.5 Conclusions 75
References 75
The Inhibitory Effect of Apolipoprotein B mRNA- Editing Enzyme Catalytic Polypeptide- Like 3G ( APOBEC3G) and Its Family Members on the Activity of Cellular MicroRNAs 80
5.1 The Antiviral Activity of APOBEC3G 81
5.2 The Translational Suppression Function of MicroRNA 82
5.3 The Role of P-bodies in Regulating the Function of MicroRNAs 84
5.4 APOBEC3G Counteracts miRNA-Mediated Repression of Protein Translation 85
5.5 Conclusion Remarks 87
References 88
MicroRNA-Mediated mRNA Deadenylation and Repression of Protein Synthesis in a Mammalian Cell- Free System 93
6.1 Introduction 94
6.2 Cell-Free Systems that Recapitulate RNA Silencing 95
6.3 Cell Extract Preparation Methodology 95
6.4 Processing of Pre-miRNA 96
6.5 In Vitro Translation Assay 97
6.6 Let-7-Mediated mRNA Deadenylation 100
6.7 Poly(A) tail and miRNA-Mediated Repression 102
6.8 Poly(A) tail and Post-Transcriptional Regulation 103
6.9 Concluding Remarks 103
References 104
miRNA Effects on mRNA Closed-Loop Formation During Translation Initiation 106
7.1 Introduction 106
7.2 Analysing Translational Repression by an miRNA 109
7.3 Towards a Model for miRNA-Mediated Translational Control 114
7.4 Concluding Remarks 116
Note Added in Proof 116
References 116
Index 120