Regulation of microRNAs (Advances in Experimental Medicine and Biology, 700)

Given this pervasiveness and importance of miRNA-mediated gene regulation, it should come as little surprise that miRNAs themselves are also highly regulated. However, the recent explosion of knowledge on this topic has been remarkable, providing a primary motivation for publication of this book. As miRNAs are transcribed by RNA polymerase II, the enzyme that also generates mRNAs, it was perhaps not unexpected that miRNA transcription would be subject to regulation, and we have willfully mitted this aspect from this monograph. However, what has been unexpected is the extent of post-transcriptional regulation of miRNAs that is illustrated in this book. Title Page 4 Copyright Page 5 PREFACE 6 ABOUT THE EDITOR... 8 PARTICIPANTS 9 Table of Contents 12 CHAPTER 1 microRNA BIOGENESIS AND FUNCTION An Overview 16 Abstract 16 INTRODUCTION: PTGS IN PLANTS AND SMALL RNAs 16 RNAi 17 DICER 17 ARGONAUTE 19 THE FIRST microRNAs AND LINKS TO RNAi 19 miRNAs: ANCIENT MEDIATORS OF GENE REGULATION 20 PRIMARY miRNA PROCESSING BY DROSHA 21 SMALL RNA SELECTIVITY OF ARGONAUTE PROTEINS 22 TARGET RECOGNITION 22 MECHANISMS OF miRNA-MEDIATED SILENCING 23 REGULATING miRNAs 25 CONCLUSION 25 REFERENCES 25 CHAPTER 2 REGULATION OF pri-miRNA PROCESSING THROUGH Smads 30 Abstract 30 INTRODUCTION: BASIC TGFβ SIGNALING 30 miRNA BIOGENESIS 32 THE FIRST PROCESSING STEP BY DROSHA 34 R-Smads REGULATE miRNA MATURATION 35 MECHANISM OF REGULATION OF SPECIFIC pri-miRNAs BY Smad 37 TRANSCRIPTIONAL REGULATION OF miRNA GENES BY SMADs 39 CONCLUSION AND FUTURE PROSPECTS 39 ACKNOWLEDGEMENT 40 REFERENCES 40 CHAPTER 3 STIMULATION OF pri-miR-18a PROCESSING BY hnRNP A1 43 Abstract 43 INTRODUCTION 43 hnRNP A1 BINDS TO THE pri-miR-18a STEM-LOOP STRUCTURE 44 hnRNP A1 PROMOTES THE DROSHA-MEDIATED PROCESSING OF pri-miR-18a 45 ROLE OF THE TERMINAL LOOPS IN miRNA PROCESSING 46 CONCLUSION AND FUTURE PROSPECTS 48 ACKNOWLEDGEMENTS 49 REFERENCES 49 CHAPTER 4 KSRP PROMOTES THE MATURATION OF A GROUP OF miRNA PRECURSORS 51 Abstract 51 INTRODUCTION 51 CO-ACTIVATORS AND CO-REPRESSORS OF miRNA PRECURSOR MATURATION 52 IMPACT OF KSRP AND OTHER CO-ACTIVATORS AND CO-REPRESSORS OF miRNA PRECURSOR MATURATION ON CELL PROLIFERATION, DIFFERENTIATION AND CANCER 54 CONCLUSION 56 REFERENCES 56 CHAPTER 5 HORMONAL REPRESSION OF miRNA BIOSYNTHESIS THROUGH A NUCLEAR STEROID HORMONE RECEPTOR 58 Abstract 58 INTRODUCTION 58 p68/p72 DEAD-BOX RNA HELICASES SERVE AS RNA-BINDING COMPONENTS IN THE DROSHA COMPLEX 59 p68/p72 RNA Helicases in RNA-Related Events 59 p68/p72 Are Components of the Large Drosha Complex 59 GENE REGULATION BY NUCLEAR ESTROGEN RECEPTORS 61 Transcriptional Control by Nuclear Estrogen Receptor 61 Transcriptional Activation by Estrogen-Bound Estrogen Receptors Requires Transcriptional Coregulators 61 Post-Transcriptional Regulation by Estrogen 63 ESTROGEN-INDUCED mRNA STABILITY IS MEDIATED THROUGH HORMONALLY REGULATED miRNA BIOSYNTHESIS 64 Activated ER􀁟 Attenuates Conversion of pri-miRNA into pre-miRNA 64 Activated ERα Suppresses Processing Activity of Drosha through Its Direct Interaction with p68/p72 64 Hormonally Down-Regulated miRNAs Stabilize VEGF mRNA in Estrogen-Dependent Breast Cancer Cells 64 CONCLUSION 67 ACKNOWLEDGEMENTS 67 REFERENCES 67 CHAPTER 6 AUTOREGULATORY MECHANISMS CONTROLLING THE MICROPROCESSOR 71 Abstract 71 INTRODUCTION 71 POST-TRANSCRIPTIONAL REGULATION OF DGCR8 BY THE MICROPROCESSOR 74 STABILIZATION OF DROSHA PROTEIN BY DGCR8 76 CONCLUSION 77 PERSPECTIVES 78 ACKNOWLEDGEMENTS 79 REFERENCES 79 CHAPTER 7 REGULATION OF pre-miRNA PROCESSING 82 Abstract 82 INTRODUCTION 82 miRNAs AND DEVELOPMENTAL TIMING IN C. ELEGANS 83 THE HETEROCHRONIC GENE lin-28 ENCODES A REGULATOR OF let-7 MICRORNA PROCESSING 84 Lin28/LIN-28 PROMOTES URIDYLATION AND DEGRADATION OF PRE-LET-7 86 HETEROCHRONIC GENE ORTHOLOGUES: ANCIENT STEM CELL REGULATORS? 86 CONCLUSION 88 ACKNOWLEDGEMENTS 89 REFERENCES 89 CHAPTER 8 THE EFFECT OF RNA EDITING AND ADARs ON miRNA BIOGENESIS AND FUNCTION 91 Abstract 91 INTRODUCTION 91 PREVALENCE OF EDITED miRNAs 93 EFFECTS OF EDITING OF pri-miRNAs AND pre-miRNAs ON BIOGENESIS 95 THE EFFECT OF EDITING ON miRNA FUNCTION 96 ADARs AS COMPETING dsRNA-BINDING PROTEINS 97 EDITING OF SEED TARGET SEQUENCES WITHIN 3'UTRs 97 CONCLUSION 98 ACKNOWLEDGEMENTS 98 REFERENCES 98 CHAPTER 9 miRNAs NEED A TRIM Regulation of miRNA Activity by Trim-NHL Proteins 100 Abstract 100 INTRODUCTION 101 THE Trim-NHL FAMILY OF DEVELOPMENTAL REGULATORS 102 THE Trim DOMAIN AS E3 UBIQUITIN LIGASE 104 FUNCTIONAL ANALYSIS OF INDIVIDUAL Trim-NHL FAMILY MEMBERS 105 Trim32 105 LIN-41 106 Trim2 and Trim3 107 Brat 108 TRIM-NHL PROTEINS AS REGULATORS OF THE miRNA PATHWAY 110 Mei-P26 110 NHL-2 111 Trim32 and the miRNA Pathway 112 mLin41 113 CONCLUSION 114 ACKNOWLEDGEMENTS 117 REFERENCES 117 CHAPTER 10 PROPERTIES OF THE REGULATORY RNA-BINDING PROTEIN HuR AND ITS ROLE IN CONTROLLING miRNA REPRESSION 121 Abstract 121 INTRODUCTION TO HuR AND ARE ELEMENTS 121 REGULATION OF THE REGULATOR 123 MOLECULAR MECHANISMS OF POST-TRANSCRIPTIONAL CONTROL BY HuR 127 FUNCTION OF HuR IN THE RELIEF OF miRNA-MEDIATED REPRESSION 129 SYNERGISM BETWEEN HuR AND let-7 IN TRANSLATIONAL REPRESSION OF c-Myc mRNA 132 CONCLUSION 133 ACKNOWLEDGEMENTS 134 REFERENCES 134 CHAPTER 11 TURNOVER OF MATURE miRNAs AND siRNAs IN PLANTS AND ALGAE 139 Abstract 139 INTRODUCTION 140 SMALL RNA PROCESSING 141 SMALL RNA MODIFICATION BY 2'-O-METHYLATION 143 SMALL RNA LOADING AND ACTIVATION OF THE RNA-INDUCED SILENCING COMPLEX 143 MATURE SMALL RNA DEGRADATION BY RIBONUCLEASES 145 QUALITY CONTROL OF MATURE SMALL RNAs 148 CONCLUSION 149 ACKNOWLEDGMENTS 151 REFERENCES 151 CHAPTER 12 MicroRNases AND THE REGULATED DEGRADATION OF MATURE ANIMAL miRNAs 155 Abstract 155 INTRODUCTION 155 microRNA BIOGENESIS AND FUNCTION 156 XRN-2, A MULTIFUNCTIONAL EXORIBONUCLEASE 158 DEGRADATION OF C. ELEGANS miRNAs BY XRN-2 159 IS miRNA TURNOVER A SUBSTRATE-SPECIFIC EVENT? 163 A FUNCTION OF XRN-2 IN miRNA TURNOVER BEYOND C. ELEGANS? 163 HALF-LIVES OF miRNAs—NOT ALL miRNAs ARE EQUAL 164 TARGET AVAILABILITY AFFECTS RELEASE OF miRNAs FROM AGO AND THEIR SUBSEQUENT DEGRADATION 166 CONCLUSION 167 ACKNOWLEDGEMENTS 167 REFERENCES 168 INDEX 171 Microrna Biogenesis And Function : An Overview / Rene F. Ketting -- Regulation Of Pri-mirna Processing Through Smads / Akiko Hata And Brandi N. Davis -- Stimulation Of Pri-mir-18a Processing By Hnrnp A1 / Gracjan Michlewski, Sonia Guil, And Javier F. Cáceres -- Ksrp Promotes The Maturation Of A Group Of Mirna Precursors / Michele Trabucchi ... [et Al.] -- Hormonal Repression Of Mirna Biosynthesis Through A Nuclear Steroid Hormone Receptor / Sally Fujiyama-nakamura, Kaoru Yamagata, And Shigeaki Kato -- Autoregulatory Mechanisms Controlling The Microprocessor / Robinson Triboulet And Richard I. Gregory -- Regulation Of Pre-mirna Processing / Nicolas J. Lehrbach And Eric A. Miska -- The Effect Of Rna Editing And Adars On Mirna Biogenesis And Function / Bret S.e. Heale, Liam P. Keegan, And Mary A. O'connell -- Mirnas Need A Trim Regulation Of Mirna Activity By Trim-nhl Proteins / F. Gregory Wulczyn ... [et Al.]. Properties Of The Regulatory Rna-binding Protein Hur And Its Role In Controlling Mirna Repression / Nicole-claudia Meisner And Witold Filipowicz -- Turnover Of Mature Mirnas And Sirnas In Plants And Algae / Heriberto Cerutti And Fadia Ibrahim -- Micrornases And The Regulated Degradation Of Mature Animal Mirnas / Helge Grobhans And Saibal Chatterjee. Edited By Helge Grosshans. Includes Bibliographical References And Index. Front Matter....Pages i-xvi microRNA Biogenesis and Function....Pages 1-14 Regulation of pri-miRNA Processing Through Smads....Pages 15-27 Stimulation of pri-miR-18a Processing by hnRNP A1....Pages 28-35 KSRP Promotes the Maturation of a Group of miRNA Precuresors....Pages 36-42 Hormonal Repression of miRNA Biosynthesis Through a Nuclear Steroid Hormone Receptor....Pages 43-55 Autoregulatory Mechanisms Controlling the Microprocessor....Pages 56-66 Regulation of pre-miRNA Processing....Pages 67-75 The Effect of RNA Editing and ADARs on miRNA Biogenesis and Function....Pages 76-84 miRNAs Need a Trim....Pages 85-105 Properties of the Regulatory RNA-Binding Protein HuR and its Role in Controlling miRNA Repression....Pages 106-123 Turnover of Mature miRNAs and siRNAs in Plants and Algae....Pages 124-139 MicroRNases and the Regulated Degradation of Mature Animal miRNAs....Pages 140-155 Back Matter....Pages 157-161