Rna Exosome

by Jensen, Torben Heick, Ph.D.

• ISBN13: 9781441978400
• ISBN10: 1441978402
• Format: Hardcover
• Copyright: 2010-12-29
• Publisher: Landes Bioscience

Summary

The diversity of RNAs inside living cells is amazing. We have known of the more 'œclassic' RNA species: mRNA, tRNA, rRNA, snRNA and snoRNA for some time now, but in a steady stream new types of molecules are being described as it is becoming clear that most of the genomic information of cells ends up in RNA. To deal with the enormous load of resulting RNA processing and degradation reactions, cells need adequate and efficient molecular machines. The RNA exosome is arising as a major facilitator to this effect. Structural and functional data gathered over the last decade have illustrated the biochemical importance of this multimeric complex and its many co-factors, revealing its enormous regulatory power. By gathering some of the most prominent researchers in the exosome field, it is the aim of the book to introduce this fascinating protein complex and to give a timely and rich account of its many functions.

Table of Contents

Finding The Exosome	p. 1
Abstract	p. 1
Introduction	p. 1
From Northerns to Nucleases	p. 2
A Glimpse of the Exosome	p. 3
The Complete Complex	p. 5
A Broader Perspective	p. 6
Conclusion	p. 6
Structural Components And Architectures of RNA Exosomes	p. 9
Abstract	p. 9
Introduction	p. 9
Global Structure of the Exosome	p. 11
RNase PH-like Domains in Bacterial, Archaeal and Eukaryotic Core Exosomes	p. 15
S1 and KH Containing Domains in Bacterial, Archaeal and Eukaryotic Core Exosomes	p. 16
Mechanism of Phosphorolytic Activity in Bacterial PNPase and Archaeal Exosomes	p. 17
Rrp44, a Eukaryotic Exosome Subunit with Hydrolytic Endoribonuclease and Processive Exoribonuclease Activities	p. 19
Rrp44 PIN Domain	p. 19
Rrp44 RNB Domain	p. 21
Rrp44 and the 10-Component Exosome	p. 22
Rrp6, a Eukaryotic Exosome Subunit with Distributive Hydrolytic Activities	p. 23
Rrp6 Interactions with the Exosome Core	p. 25
Conclusion	p. 25
The Archaeal Exosome	p. 29
Abstract	p. 29
Introduction	p. 29
Core Subunits of the Archaeal Exosome	p. 30
Structure and Mechanism	p. 31
Physiological Functions	p. 35
Conclusion	p. 36
The Exosomes of Trypanosomes And Other Protists	p. 39
Abstract	p. 39
Introduction: Why Study the Exosomes of Organisms Other Than Yeast and Animals?	p. 39
Trypanosomes as a Model System for RNA Processing and Turnover	p. 40
The Structure of the Trypanosome Exosome	p. 41
The Position of RRP6 Relative to the Exosome Core	p. 41
Functions of the Trypanosome Exosome in the Nucleus	p. 43
Functions of the Trypanosome Exosome in the Cytoplasm	p. 44
Conservation of the Exosome in Eukaryotic Evolution	p. 46
Conclusion	p. 47
The Exosome And 3′-5′ RNA Degradation in Plants	p. 50
Abstract	p. 50
Introduction	p. 50
Composition of Plant Exosome Core Complexes	p. 51
Functional Specialisation of Individual Subunits?	p. 53
Exosome Cofactors and Auxiliary Proteins in Plants	p. 55
RNA Substrates of the Plant Exosome Complex	p. 56
Impact of 3′-5′ RNA Decay on Plant Genome Expression	p. 57
Impact of 3′-5′ Degradation in Organelles	p. 58
Conclusion	p. 59
Catalytic Properties of the Eukaryotic Exosome	p. 63
Abstract	p. 63
Introduction	p. 63
Exosome Composition	p. 64
DIS3	p. 66
Rrp6	p. 71
Holoenzyme Activities	p. 71
Noncatalytic Activities of the Exosome Ring	p. 74
Conclusion	p. 76
Functions of The Cytoplasmic Exosome	p. 79
Abstract	p. 79
Introduction	p. 79
The Cytoplasmic Exosome Requires Four Cofactors	p. 80
The Exosome Functions in One of Two General Pathways for Cytoplasmic mRNA Degradation	p. 82
The Cytoplasmic Exosome Functions in mRNA Surveillance	p. 83
The Antiviral Function of the Cytoplasmic Exosome	p. 85
Conclusion and Future Perspectives	p. 86
Rrp6, Rrp477 And Cofactors of the Nuclear Exosome	p. 91
Abstract	p. 91
Introduction	p. 91
Structure and Activity of Rrp6	p. 92
The Role of Rrp6 in the Maturation of Noncoding RNAs	p. 93
The Role of Rrp6 in mRNA Surveillance	p. 94
The Role of Rrp6 in the Regulation of mRNA Levels	p. 94
Rrp6 and the TRAMP Complex	p. 95
The Exosome Cofactor Rrp47	p. 96
Structure of Rrp47	p. 96
Biochemical Activities of Rrp47	p. 97
The Role of Rrp47 in RNA Processing and Degradation	p. 97
The Exosome Cofactor Mpp6	p. 99
Conclusion	p. 100
The Exosome And Heterochromatin: Multilevel Regulation of Gene Silencing	p. 105
Abstract	p. 105
Introduction	p. 105
Heterochromatin	p. 106
Gene Silencing Pathways: RNAi and the Exosome	p. 108
Multilevel Regulation of Gene Expression	p. 112
Regulating the Regulators: How the Stability of ncRNAs Determines Their Function in Heterochromatin Formation	p. 114
Conclusion	p. 117
Control of Cryptic Transcription in Eukaryotes	p. 122
Abstract	p. 122
Introduction: New Perspectives on the Shape of the Transcriptome	p. 122
A Dedicated Pathway of Nuclear RNA Degradation	p. 123
Widespread Transcription in Eukaryotic Genomes	p. 124
Transcription Termination and the Hallmark of CUTs Instability	p. 125
An RNAPII "CTD Code" for the Fate of Nascent Transcripts	p. 126
Regulatory Roles of Cryptic Transcription	p. 128
Conclusion	p. 129
The Human Exosome And Disease	p. 132
Abstract	p. 132
Introduction	p. 132
Identification of the PM/Scl Complex	p. 133
Autoantibodies to the Exosome / PM/Scl-Antigen	p. 134
Initiation of the Anti-Exosome / PM/Scl Autoimmune Response	p. 137
The Human Exosome and Cancer	p. 138
Conclusion	p. 139
Index	p. 143
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