Eukaryotic RNases and their Partners in RNA Degradation and Biogenesis

Preface

Chapter One. Dicer Proteins and Their Role in Gene Silencing Pathways

1. Introduction

2. Dicers: RNase III Family Members with a Role in Gene Silencing

3. Mechanism of Processing and the Role of the Catalytic RNase III Domains

4. Role of Other Domains in Dicer Function

5. Domain Arrangement in Metazoan Dicers

6. Inside-Out Processing Mechanism by the Yeast Dicer

7. Function of Dicer in the Nucleus

8. Proteins Interacting with Dicer and the Assembly of RISC Effector Complexes

9. Future Perspectives

References

Chapter Two. Loquacious, a Dicer Partner Protein, Functions in Both the MicroRNA and siRNA Pathways

1. Introduction

2. miRNA and siRNA Pathways in the Fruit Fly Drosophila melanogaster

3. Drosophila Dicer-1 and Dicer-2: Similar but Distinct Domain Structures

4. Conserved Partnerships Between Dicer and Dicer-Binding Partner dsRBD Proteins

5. loqs Encodes Four Alternatively Spliced Isoforms

6. Loqs-PA and Loqs-PB Bind to Dicer-1, While Loqs-PD and R2D2 Bind to Dicer-2

7. Partner Protein Mutant Phenotypes in Flies and Mammals

8. Loqs-PA and Loqs-PB Function in the miRNA Pathway

9. Loqs-PD Functions in the siRNA Pathway

10. Loqs-PB Is Required to Maintain Ovarian Germline Stem Cells

11. For Some miRNAs, Loqs-PB Tunes Mature miRNA Length

12. Future Directions

13. Concluding Remarks

References

Chapter Three. Translin: TRAX Complex (C3PO), a Novel Ribonuclease for the Degradation of Small RNAs

1. Introduction: Earlier Studies of Translin and TRAX

2. Discovery of C3PO as a Novel Endoribonuclease Involved in the Activation of RNA-Induced Silencing Complex

3. C3PO Ribonuclease in tRNA Processing

4. Structure of C3PO: An Unusual Asymmetrical Hetero-Octamer

5. Oligomeric States of C3PO and Implications for Substrate Binding and Activation

6. Enzymatic Properties of C3PO

7. Concluding Remarks

References

Chapter Four. Structure and Mechanism of Argonaute Proteins

1. Introduction

2. Basic Argonaute Architecture

3. Recognition of the Guide 5′-end by the MID Domain

4. Preorganization of the Seed Facilitates Target Recognition

5. Recognition of the Guide RNA 3′-end by the PAZ Domain

6. The Two-State Model of Target Binding

7. The Rubber Band Model of RISC Loading

8. The Slicer Active Site Resides in the PIWI Domain

9. Recruitment of Silencing Factors

References

Chapter Five. Drosha and DGCR8 in MicroRNA Biogenesis

1. Introduction

2. Drosha

3. DGCR8 as the RNA-Binding Partner of Drosha

4. DGCR8 as a Heme Protein

5. DGCR8 in DiGeorge Syndrome

6. How do DGCR8 and Drosha Structurally Recognize Pri-miRNAs?

7. How Is Pri-miRNA Processing Regulated?

8. Drosha and DGCR8 Bind RNAs Other Than Pri-miRNAs

9. Future Perspectives

References

Chapter Six. Control of Drosha-Mediated MicroRNA Maturation by Smad Proteins

1. miRNA Biogenesis

2. Drosha and DGCR8

3. Modulators of the Drosha Microprocessor Complex

4. Smad Proteins

5. miRNA Regulation by Smads

6. Closing Remark

References

Chapter Seven. PIWI Proteins and Their Slicer Activity in piRNA Biogenesis and Transposon Silencing

1. Introduction

2. Drosophila PIWI Proteins

3. piRNA Biogenesis

4. Outstanding Questions

References

Chapter Eight. Control of MicroRNA Maturation by p53 Tumor Suppressor and MCPIP1 Ribonuclease

1. Introduction

2. Two-Step Endoribonuclease Reactions in miRNA Maturation

3. Control of miRNA Biosynthesis by p53

4. Negative Regulation of miRNA Processing by MCPIP1

5. Autoregulation of miRNA Processing Processes

6. Alteration of miRNA Biogenesis in Human Cancer

7. Conclusion

References

Chapter Nine. Nanoparticle-Based Delivery of siRNA and miRNA for Cancer Therapy

1. Introduction

2. Potential Use of siRNAs and miRNAs for Cancer Therapy

3. Nanoparticle-Based Delivery

4. Summary and Future Prospects

References

Author Index

Subject Index