Nonsense-Mediated mRNA Decay

296 Pages·2006·40.94 MB·\296

by  Lynne E. Maquat (Author)

Molecular Biology
Intelligence
Unit
Nonsense-Mediated
mRNA Decay
Lynne E. Maquat, Ph.D.
Department of Biochemistry and Biophysics
School of Medicine and Dentistry
University of Rochester
Rochester, New York, U.S.A.
Boca Raton London New York
CRC Press is an imprint of the
Taylor & Francis Group, an informa business
NONSENSE-MEDIATED MRNA DECAY
Molecular Biology Intelligence Unit
First published 2006 by Landes Bioscience
Published 2018 by CRC Press
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© 2006 by Taylor & Francis Group, LLC
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About the Editor...
LYNNE E. MAQUAT, Ph.D., is Professor of Biochemistry and Biophysics at
the University of Rochester School of Medicine and Dentistry in Rochester, New
York. She has studied nonsense-mediated mRNA decay since 1980, beginning
with characterizations of patients having the hemolytic anemias ß°-thalassemia
and triosephosphate isomerase deficiency. She is currently President of the RNA
Society and member of the Public Information Committee of the American
Society for Cell Biology. Dr. Maquat is on the editorial board of Molecular &
Cellular Biology у RNA, RNA Biology, and Faculty of1000, and was formerly chair
of the National Institutes of Health CDF-1 study section. At the University of
Rochester, she is Director of Graduate Women in Science. She has been selected
by the New York State Commissioner of Health as an exemplary scientist and
received the Davey Award for outstanding cancer research. Her extracurricular
activities include trekking in Ladakh, Nepal, Tibet and other remote places, and
fund-raising for the arts community.
Dedication
To Mark and Lily, previous and current members of my
lab, co-workers in NMD and related fields, and readers who
just wish to know.
CONTENTS
Preface.....................................................................................................................XV
Section I: Saccharomyces cerevisiae.....................................................................1
1. Features of Nonsense-Mediated mRNA Decay
in Saccharomyces cerevisiae...........................................................................3
Kristian E. Baker and Roy Parker
Nonsense-Mediated Decay Targets Aberrant RNA Transcripts................3
Translational Termination: Discrimination between Normal
versus Aberrant mRNA...................................................................................4
Translation Termination and mRNP Organization......................................4
Aberrant mRNA Definition Leads to Translational
Repression and Accelerated RNA Degradation.........................................6
Decay of NMD Substrates May Occur in Cytoplasmic Foci
Termed P Bodies...............................................................................................8
Position-Dependent NM D.................................................................................9
Physical Interactions between NMD, Translation
and Decay Machineries...................................................................................9
Spatial and Temporal Recognition of NMD Substrates............................10
Conclusions...........................................................................................................10
2. All Termination Events Are Not Equal:
Premature Termination in Yeast Is Aberrant
and Triggers NMD.....................................................................................15
Nadia Amrani and Allan Jacobson
Quality Control of Translation Termination.............................................. 15
Factors Regulating Translation Termination and NMD......................... 16
A Role for the Upf/Nmd Factors in Translation Termination.................16
Pathways for Decay of Yeast Nonsense-Containing mRNAs:
A Requirement for Ongoing Translation................................................ 17
NMD Regulation by cis-Acting Elements....................................................18
Models: Surveillance Complex vs Faux UTR.............................................. 18
Translation Termination at Premature Nonsense Codons
Is Aberrant........................................................................................................18
З'-UTR Mimicry Reestablishes Normal Rates
of mRNA Decay..............................................................................................20
A Higher Resolution Faux UTR Model for NM D....................................20
3. Endogenous Substrates of the Yeast NMD Pathway..............................27
Feng He and Allan Jacobson
Historical Perspective.........................................................................................27
NMD Substrate Identification by Genome-Wide
Expression Profiling.......................................................................................29
Further Attributes of NMD Substrates..........................................................36
Concluding Remarks..........................................................................................37
Section II: Mammals...................................... 43
4. NMD in Mammalian Cells: A History....................................................45
Lynne E. Maquat
In the Beginning.................................................................................................45
NMD Targets Newly Synthesized mRNA:
The Role of Intron Position........................................................................46
NMD Generally Requires a Post-Splicing Exon Junction
Complex Downstream of the Site of Translation Termination........48
Evidence That NMD Is Restricted to CBP80-Bound mRNA
and Does Not Detectably Target eIF4E-Bound mRNA:
The Pioneer Translation Initiation Complex..........................................52
Evidence That NMD Degrades mRNA from Both 5' and 3' Ends......53
The Importance of NM D.................................................................................54
Future Frontiers..................................................................................................54
5. Human Upf Proteins in NMD..................................................................59
Guramrit Singh and Jens Lykke-Andersen
Evidence That Upf Proteins Are Involved in the Human
NMD Pathway................................................................................................59
hUpfl Is a RNA Helicase and a Phosphoprotein......................................60
hUpf2 and hUpf3 Function in NM D...........................................................61
Interactions between hUpf Proteins................................................................61
Interactions between hUpf Proteins and the Translation Machinery ... 62
hUpf Proteins Are Recruited to mRNAs.......................................................63
hUpf Proteins Help Discriminate PTC-Containing
from Normal mRNAs...................................................................................64
hUpf Proteins Trigger mRNA Decay............................................................65
Conclusions and Future Perspectives.............................................................66
6. NMD and the Immune System.................................................................71
Jayanthi P. Gudikote and Miles F. Wilkinson
Ig and TCR Gene Rearrangements Frequently Generate
Nonsense Codons...........................................................................................71
NMD and Immune Receptors........................................................................73
The Second Signal for NM D..........................................................................74
Unique Features of Ig and TCR NM D........................................................75
Physiological Relevance and the Future.........................................................80
7. Role of SMG-1-Mediated Phosphorylation of Upfl in NMD...............85
Akio Yamashita, Isao Kashima and Shigeo Ohno
Structure and Biochemical Characterization of SMG-1 ............................86
SMG-1-Mediated Phosphorylation of Upfl................................................87
Mechanism of SMG-1-Mediated Phosphorylation of Upfl.....................87
Consequences of SMG-1-Mediated Phosphorylation of Upfl................92
Regulation of SMG-1-Mediated Upfl Phosphorylation...........................93
Suppression of SMG-1-Mediated Upfl Phosphorylation
Inhibits NMD.................................................................................................93
Perspectives...........................................................................................................94
8. Physiologie Substrates and Functions for Mammalian NMD...............97
Neda A. Sharifi and Harry C. Dietz
Lessons from Lower Eukaryotes.......................................................................97
Mammalian NMD..............................................................................................99
Conclusions and Perspectives.........................................................................106
9. NMD and Human Disease.....................................................................Ill
Jill A. Holbrooky Gabriele Neu-Yiliky Matthias W. Hentze
and Andreas E. Kulozik
“NMD-Neutral” PTCs...................................................................................Ill
NMD-Mediated Protection of Heterozygotes:
The Example of ß-Thalassemia................................................................ Ill
NMD in Acquired Genetic Conditions..................................................... 114
Medical Therapies for PTC-Related Disease..............................................116
Conclusions....................................................................................................... 117
10. Therapies of Nonsense-Associated Diseases.......................................121
Kim M. Keeling, Ming Du and David M. Bedwell
Suppression of Premature Stop Mutations..................................................121
Aminoglycoside-Mediated Nonsense Suppression....................................122
Other Pharmacological Compounds That Suppress
Nonsense Mutations.....................................................................................126
Suppression of Nonsense Mutations Using Suppressor tRNAs...........126
Mutation Repair.................................................................................................127
Suppression of NMD.......................................................................................127
Future Development of Therapies for Nonsense-Associated
Diseases............................................................................................................130
Section III: Caenorhabditis elegans............................................................... 137
11. NMD in Caenorhabditis elegans...............................................................139
Philip Anderson
Discovery of C. elegans Mutants Defective for NM D..............................139
SMG Proteins Are Conserved among Eukaryotes...................................141
NMD Requires a Cycle of SMG-2 Phosphorylation................................142
Biological Functions of NMD........................................................................143
Section IV: Drosophila melanogaster........................................................... 151
12. NMD in Drosophila: A Snapshot into the Evolution
of a Conserved mRNA Surveillance Pathway.........................................153
Isabelle Behm-Ansmant and Elisa Izaurralde
The NMD Protein Interaction Network: An Overview..........................154
Mechanism of PTC Definition in Drosophila.......................................... 156
Decay of NMD Targets in Drosophila.........................................................157
Evolution of the Physiological Role of NM D............................................158
Perspectives.........................................................................................................160
Section V: Plants.............................................................................................. 165
13. NMD in Plants..........................................................................................167
Ambro van Hoof and Pamela J. Green
NMD Is Widespread in Plants.......................................................................167
To Be Premature or Not Premature, That Is the Question..................168
Conserved trans-Acting Factors in NM D...................................................169
Concluding Remarks...................................................................................... 171
Section VI: Evolutionary Aspects of NMD..................................................173
14. Regulation of Gene Expression by Coupling
of Alternative Splicing and NMD............................................................175
David A. W. Soergel, Liana F. Lareau and Steven E. Brenner
Alternative Splice Forms Are Frequently Targets of NM D....................176
Constitutive Unproductive Splicing.............................................................184
Regulated Unproductive Splicing.................................................................185
Autoregulatory Unproductive Splicing........................................................188
Conservation of RUST....................................................................................190
Why RUST?........................................................................................................190
15. NMD and the Evolution of Eukaryotic Gene Structure......................197
Michael Lynch, Xin Hong, and Douglas G. Scofield
Sources of Inappropriate Transcripts...........................................................198
Phylogenetic Roots of NMD.........................................................................200
NMD and the Proliferation of Introns.......................................................206
Section VII: Roles for NMD Factors Other Than in NMD.....................213
16. The SMG-1 Kinase: At the Crossroads of mRNA Surveillance
and Stress Response Pathways.................................................................215
Robert T Abraham and Vasco Oliveira
Structural Features of SMG-1 and Related Kinases..................................216
Characterizing hSMG-1 Kinase Activity.....................................................218
Roles of hSMG-1 in NM D............................................................................220
Cytoprotective Functions of hSMG-1 ........................................................221
Anti-Apoptotic Functions of hSMG-1.........................................................222
Conclusions and Perspectives........................................................................224
17. Staufen 1-Mediated mRNA Decay: A Upfl-Dependent Pathway.......229
Yoon Ki Kim and Lynne E. Maquat
Human Upfl Interacts with Human Staufen 1 .........................................229
Staul Binding to the 3' Untranslated Region of an mRNA
Reduces mRNA Abundance Independently of an EJC......................230
mRNAs That Bind Staul within Their 3' Untranslated
Regions Are Subject to SMD.....................................................................232
The Relationship between NMD and SMD..............................................233
Future Directions..............................................................................................233
18. Upfl Regulates Mammalian Histone mRNA Decay...........................237
Handan Kaygun and William F. Marzluff
Regulation of Histone mRNA Half-Life.....................................................237
NMD and Histone mRNA Degradation....................................................239
Translation Is Required for Histone mRNA Degradation.....................239
The Position of the Stem-Loop Is a Critical Determinant
of Histone mRNA Stability.......................... 241
Upfl Is Required for Rapid Degradation of Histone mRNA..............243
SLBP Helps the Recruitment of Upfl to the 3' End
of Histone mRNAs.......................................................................................244
Role of the DNA Damage Checkpoint Pathway
in Regulated Histone mRNA Degradation............................................244
Is the Mechanism of Histone mRNA Degradation
Like NMD in Yeast?....................................................................................246
Signals That Activate Histone mRNA Degradation.................................246
Upfl Action in Histone mRNA Degradation..........................................247
19. S. cerevistae Esti///, sapiens SMG6 Protein Family Members
Function in Telomere Metabolism..........................................................253
Claus M. AzzaltHy Sophie Redon and Joachim Lingner
Esti Protein in S. cerevisiae.............................................................................254
Discovery of Esti Homologs.........................................................................254
Sc Esti Homologs and Telomere Maintenance........................................255
Hs ESTI A, В and C Are Identical to NMD Factors
Hs SMG6, 5 and 7 .......................................................................................258
The ESTl-TPR Domain Has a 14-3-3 Fold.............................................258
Conclusion..........................................................................................................259
20. Nonsense-Associated Altered Splicing....................................................263
Zuo Zhang and Adrian R. Krainer
Examples That Support NAS........................................................................264
Examples That Do Not Support NAS.........................................................266
Conclusions.........................................................................................................269
Index...........................................................................................................273