miRNA Regulation of the Translational Machinery

miRNA Regulation of the Translational Machinery

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The silencing of gene expression by small interfering RNAs has been recognized for only a relatively short time, but this has transformed our understanding of both transcriptional and post-transcriptional gene regulatory mechanisms. Multiple pathways culminate in formation of an RNA-induced silencing complex (RISC) containing a member of the Argonaute protein family bound to a 22-nt RNA strand that interacts with a target mRNA or gene through Watson-Crick base pairing. One consequence is mRNA-specific inhibition of protein synthesis. Evidence has been presented for diverse mechanisms, but there is not universal agreement in the field of how RISCs affect the translational machinery. The chapters collected in this volume represent contribution by leaders in the search to understand how miRNAs affect translation. They include chapters representing work in plants and Caenorhabditis elegans, the biological systems that originally led to the discovery of small interfering RNAs, but also include chapters on mammalian systems, with special emphasis on regulation of a key tumor suppressor and a protein that restricts human immunodeficiency virus 1 (HIV-1).

1;Preface;6 2;Contents;8 3;Contributors;9 4;Understanding How miRNAs Post- Transcriptionally Regulate Gene Expression;11 4.1;1.1 Introduction;12 4.2;1.2 miRNA Biogenesis;15 4.3;1.3 miRNA-Mediated Regulation of Eukaryotic Gene Expression;17 4.4;1.4 Summary;25 4.5;References;25 5;Translational Control of Endogenous MicroRNA Target Genes in C. elegans;31 5.1;2.1 Introduction;32 5.2;2.2 lin-4 and let-7 miRNAs in C. elegans Development;32 5.3;2.3 Polysome Profiling as an Assay to Assess the Translational State of mRNAs;34 5.4;2.4 MicroRNA-Mediated Gene Regulation in C. elegans: The Early View;35 5.5;2.5 MicroRNA Mediated Gene Regulation in Other Model Organisms;36 5.6;2.6 The let-7 miRNA Extensively Interacts with Translation Factors;40 5.7;2.7 Polysome Profiling Confirms Translational Repression at the Initiation Step in C. elegans;41 5.8;2.8 Inhibition of Translation Initiation and Transcript Degradation Both Depend on the GW182 Proteins AIN-1 and AIN- 2;44 5.9;2.9 Conclusions and Future Perspectives;46 5.10;References;47 6;Translational Inhibition by MicroRNAs in Plants;51 6.1;3.1 Introduction;52 6.2;3.2 miRNA and siRNA Biogenesis;52 6.3;3.3 ARGONAUTE Proteins;54 6.4;3.4 Translational Inhibition by Small RNAs is Common in Plants;55 6.5;3.5 Roles of miRNA-Mediated Translational Inhibition in Plants;58 6.6;3.6 Conclusion;62 6.7;References;63 7;Regulation of p27kip1 mRNA Expression by MicroRNAs;68 7.1;4.1 Introduction;68 7.2;4.2 miRNAs in Cancer;69 7.3;4.3 Role of p27 in Tumor Progression;71 7.4;4.4 Regulation of p27 Expression: Role of miRNAs;72 7.5;4.5 Conclusions;75 7.6;References;75 8;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 8.1;5.1 The Antiviral Activity of APOBEC3G;81 8.2;5.2 The Translational Suppression Function of MicroRNA;82 8.3;5.3 The Role of P-bodies in Regulating the Function of MicroRNAs;84 8.4;5.4 APOBEC3G Counteracts miRNA-Mediated Repression of Protein Translation;85 8.5;5.5 Conclusion Remarks;87 8.6;References;88 9;MicroRNA-Mediated mRNA Deadenylation and Repression of Protein Synthesis in a Mammalian Cell- Free System;93 9.1;6.1 Introduction;94 9.2;6.2 Cell-Free Systems that Recapitulate RNA Silencing;95 9.3;6.3 Cell Extract Preparation Methodology;95 9.4;6.4 Processing of Pre-miRNA;96 9.5;6.5 In Vitro Translation Assay;97 9.6;6.6 Let-7-Mediated mRNA Deadenylation;100 9.7;6.7 Poly(A) tail and miRNA-Mediated Repression;102 9.8;6.8 Poly(A) tail and Post-Transcriptional Regulation;103 9.9;6.9 Concluding Remarks;103 9.10;References;104 10;miRNA Effects on mRNA Closed-Loop Formation During Translation Initiation;106 10.1;7.1 Introduction;106 10.2;7.2 Analysing Translational Repression by an miRNA;109 10.3;7.3 Towards a Model for miRNA-Mediated Translational Control;114 10.4;7.4 Concluding Remarks;116 10.5;Note Added in Proof;116 10.6;References;116 11;Index;120
ISBN 9783642031038
Artikelnummer 9783642031038
Medientyp E-Book - PDF
Auflage 2. Aufl.
Copyrightjahr 2009
Verlag Springer-Verlag
Umfang 115 Seiten
Sprache Englisch
Kopierschutz Digitales Wasserzeichen