ABOUT THIS BOOK
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.
Content Level » Research
Keywords » Großhans - RNA - Regulation - micro - microRNA
Related subjects » Biomedical Sciences - Human Genetics
Helge Großhans, PhD is a research group leader at the Friedrich Miescher Institute for Biomedical Research (FMI), which is part of the Novartis Research Foundation in Basel, Switzerland. His main research interests are in the developmental function, regulation, and mechanism of action of microRNAs. He received his PhD from the University of Heidelberg and did his postdoctoral training at Yale University. He is the winner of a 2009 ERC Award.
TABLE OF CONTENTS
1. microRNA BIOGENESIS AND FUNCTION - AN OVERVIEW René F. Ketting Abstract Introduction: PTGS in Plants and Small RNAs RNAi Dicer Argonaute The First microRNAs and Links to RNAi miRNAs: Ancient Mediators of Gene Regulation Primary miRNA Processing by Drosha Small RNA Selectivity of Argonaute Proteins Target Recognition Mechanisms of miRNA-Mediated Silencing Regulating miRNAs Conclusion 2. REGULATION OF pri-miRNA PROCESING THROUGH Smads Akiko Hata and Brandi N. Davis Abstract Introduction: Basic Tgfß Signaling miRNA Biogenesis The First Processing Step by Drosha R-Smads Regulate miRNA Maturation Mechanism of Regulation of Specific pri-miRNAs by Smad Transcriptional Regulation of miRNA Genes by Smads Conclusion and Future Prospects 3. STIMULATION OF pri-miR-18a PROCESING BY hnRNP A1 Gracjan Michlewski, Sonia Guil and Javier F. Cáceres Abstract Introduction hnRNP A1 Binds to The pri-miR-18a Stem-Loop Structure hnRNP A1 Promotes The Drosha-Mediated Processing of pri-miR-18a Role of The Terminal Loops in miRNA Processing Conclusion and Future Prospects 4. KSRP PROMOTES THE MATURATION OF A GROUP OF miRNA PRECURSORS Michele Trabucchi, Paola Briata, Witold Filipowicz, Andres Ramos, Roberto Gherzi and Michael G. Rosenfeld Abstract Introduction Co-Activators and Co-Repressors of miRNA Precursor Maturation Impact of KSRP and Other Co-Activators and Co-Repressors of miRNA Precursor Maturation on Cell Proliferation, Differentiation and Cancer Conclusion 5. Hormonal Repression of mirna Biosynthesis Through a Nuclear Steroid Hormone Receptor Sally Fujiyama-Nakamura, Kaoru Yamagata and Shigeaki Kato Abstract Introduction p68/p72 DEAD-Box RNA Helicases Serve as RNA-Binding Components in the Drosha Complex Gene Regulation by Nuclear Estrogen Receptors Estrogen-Induced mRNA Stability is Mediated through Hormonally Regulated miRNA Biosynthesis Conclusion 6. Autoregulatory mechanisms controlling the Microprocessor Robinson Triboulet and Richard I. Gregory Abstract Introduction Posttranscriptional Regulation of DGCR8 by the Microprocessor Stabilization of Drosha Protein by DGCR8 Conclusion 7. Regulation of pre-miRNA processing Nicolas J. Lehrbach and Eric A. Miska Abstract Introduction miRNAs and Developmental Timing in C. elegans The Heterochronic Gene lin-28 encodes a Regulator of let-7 microRNA Processing Lin28/LIN-28 Promotes Uridylation and Degradation of Pre-let-7 Heterochronic Gene Orthologues: Ancient Stem Cell Regulators? Conclusion 8. THE EFECT OF RNA EDITING AND ADARs ON miRNA BIOGENESIS AND FUNCTION Bret S.E. Heale, Liam P. Keegan and Mary A. O’Connell Abstract Introduction Prevalence of Edited miRNAs Effects of Editing of pri-miRNAs and pre-miRNAs on Biogenesis The Effect of Editing on miRNA Function ADARs as Competing dsRNA-Binding Proteins Editing of Seed Target Sequences within 3'UTRs Conclusion 9. miRNAs need a Trim Regulation of miRNA Activity by Trim-NHL Proteins F. Gregory Wulczyn, Elisa Cuevas, Eleonora Franzoni and Agnieszka Rybak Abstract Introduction The Trim-NHL Family of Developmental Regulators The Trim Domain as E3 Ubiquitin Ligase Functional Analysis of Individual Trim-NHL Family Members Trim-NHL Proteins as Regulators of the miRNA Pathway Conclusion 10. Properties of the Regulatory RNA-Binding Protein HuR and its Role in Controlling miRNA Repression Nicole-Claudia Meisner and Witold Filipowicz Abstract Introduction to HuR and ARE Elements Regulation of the Regulator Molecular Mechanisms of Posttranscriptional Control by HuR Function of HuR in the Relief of miRNA-Mediated Repression Synergism between HuR and let-7 in Translational Repression of c-Myc mRNA Conclusion 11. Turnover of Mature miRNAs and siRNAs in Plants and Algae Heriberto Cerutti and Fadia Ibrahim Abtract Introduction Small RNA Processing Small RNA Modification by 2'-O-Methylation Small RNA Loading and Activation of the RNA-Induced Silencing Complex Mature Small RNA Degradation by Ribonucleases Quality Control of Mature Small RNAs Conclusion 12. MicroRNases and the regulated degradation of mature animal miRNAs Helge Großhans and Saibal Chatterjee Abstract Introduction microRNA Biogenesis and Function XRN-2, a Multifunctional Exoribonuclease Degradation of C. elegans miRNAs by XRN-2 Is miRNA Turnover a Substrate-Specific Event? A Function of XRN-2 in miRNA Turnover beyond C. elegans? Half-Lives of miRNAs—Not all miRNAs are Equal Target Availability Affects Release of miRNAs from AGO and their Subsequent Degradation Conclusion Index