Research Topics
Genomes and Genes | Witold FilipowiczSummaryAffiliation: Friedrich Miescher Institute Country: Switzerland Publications
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Publications
The liver-specific microRNA miR-122: biology and therapeutic potentialWitold Filipowicz
Friedrich Miescher Institute for Biomedical Research, Basel CH 4002, Switzerland
Prog Drug Res 67:221-38. 2011..We discuss antisense strategies targeting miR-122 as a potential therapeutic approach to treat hepatitis C and possibly other diseases...- Biogenesis of small nucleolar ribonucleoproteinsWitold Filipowicz
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH 4058 Basel, Switzerland
Curr Opin Cell Biol 14:319-27. 2002..Cajal bodies emerge as nuclear structures important for the biogenesis and function of small nucleolar ribonucleoproteins... 
Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?Witold Filipowicz
Friedrich Miescher Institute for Biomedical Research, 4002 Basel, Switzerland
Nat Rev Genet 9:102-14. 2008..This Review summarizes the current understanding of the mechanistic aspects of microRNA-induced repression of translation and discusses some of the controversies regarding different modes of microRNA function...- Single processing center models for human Dicer and bacterial RNase IIIHaidi Zhang
Friedrich Miescher Institute for Biomedical Research, PO Box 2543, 4002 Basel, Switzerland
Cell 118:57-68. 2004..Based on these and other data, we propose that Dicer functions through intramolecular dimerization of its two RNase III domains, assisted by the flanking RNA binding domains, PAZ and dsRBD... 
TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts with Dicer and functions in RNA silencingAstrid D Haase
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4508 Basel, Switzerland
EMBO Rep 6:961-7. 2005..The TRBP-Dicer interaction shown raises interesting questions about the potential interplay between RNAi and interferon-PKR pathways...- The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA functionInga Loedige
Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland
Nucleic Acids Res 41:518-32. 2013.... - miRNA repression involves GW182-mediated recruitment of CCR4-NOT through conserved W-containing motifsMarina Chekulaeva
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
Nat Struct Mol Biol 18:1218-26. 2011.... - Dicer is associated with ribosomal DNA chromatin in mammalian cellsLasse Sinkkonen
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
PLoS ONE 5:e12175. 2010..Components of the RNA silencing machinery are involved in different aspects of chromatin function in numerous organisms. However, association of RNA silencing with chromatin in mammalian cells remains unclear... - Effects of Dicer and Argonaute down-regulation on mRNA levels in human HEK293 cellsDaniela Schmitter
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4002 Basel, Switzerland
Nucleic Acids Res 34:4801-15. 2006..Taken together, our data suggest that, independent of the effect on translation, miRNAs affect levels of a few hundred mRNAs in HEK293 cells... - MicroRNAs control de novo DNA methylation through regulation of transcriptional repressors in mouse embryonic stem cellsLasse Sinkkonen
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland
Nat Struct Mol Biol 15:259-67. 2008..The defective DNA methylation can be rescued by ectopic expression of de novo Dnmts or by transfection of the miR-290 cluster miRNAs, indicating that de novo DNA methylation in ES cells is controlled by miRNAs... - Inhibition of translational initiation by Let-7 MicroRNA in human cellsRamesh S Pillai
Friedrich Miescher Institute for Biomedical Research, 4002 Basel, Switzerland
Science 309:1573-6. 2005..Repressed mRNAs, Ago proteins, and miRNAs were all found to accumulate in processing bodies. We propose that localization of mRNAs to these structures is a consequence of translational repression... - Post-transcriptional gene silencing by siRNAs and miRNAsWitold Filipowicz
Friedrich Miescher Institute for Biomedical Research, PO Box 2543, 4002 Basel, Switzerland
Curr Opin Struct Biol 15:331-41. 2005..The first structural information on protein components of the RNA interference (RNAi) and miRNA machineries is emerging, and provides some insight into the mechanism of RNA-silencing reactions... - Kinetic analysis reveals successive steps leading to miRNA-mediated silencing in mammalian cellsJulien Béthune
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland
EMBO Rep 13:716-23. 2012..This step is followed by mRNA deadenylation and decay, which is the dominant effect at steady state. Our findings have important implications for understanding the mechanism of silencing and reconcile seemingly contradictory data... - Human dicer: purification, properties, and interaction with PAZ PIWI domain proteinsFabrice A Kolb
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
Methods Enzymol 392:316-36. 2005..In this chapter we describe overexpression and purification of recombinant human Dicer, its biochemical properties, and mapping of domains responsible for Dicer-PPD protein interactions... - Argonautes and company: sailing against the windSuvendra N Bhattacharyya
Friedrich Miescher Institute for Biomedical Research, 4002 Basel, Switzerland
Cell 128:1027-8. 2007..AGO2 and FXR1 bind to the AU-rich element in the 3'-UTR of TNFalpha mRNA, unexpectedly activating its translation in a cell growth-dependent manner... - Relief of microRNA-mediated translational repression in human cells subjected to stressSuvendra N Bhattacharyya
Friedrich Miescher Institute for Biomedical Research, P.O. Box 2543, 4002 Basel, Switzerland
Cell 125:1111-24. 2006..We propose that proteins interacting with the 3'UTR will generally act as modifiers altering the potential of miRNAs to repress gene expression... - The GW/WG repeats of Drosophila GW182 function as effector motifs for miRNA-mediated repressionMarina Chekulaeva
Friedrich Miescher Institute for Biomedical Research, 4002 Basel, Switzerland
Nucleic Acids Res 38:6673-83. 2010..These results demonstrate a novel role for the GW/WG repeats as effector motifs in miRNA-mediated repression... - Importance of the C-terminal domain of the human GW182 protein TNRC6C for translational repressionJakob T Zipprich
Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland
RNA 15:781-93. 2009..Through deletion and mutagenesis, we identified the C-terminal part of TNRC6C encompassing the RRM RNA-binding motif as a key effector domain mediating protein synthesis repression by TNRC6C... - Role of Dicer in posttranscriptional RNA silencingLukasz Jaskiewicz
Friedrich Miescher Institute for Biomedical Research, 4002 Basel, Switzerland
Curr Top Microbiol Immunol 320:77-97. 2008..We also discuss information about Dicer-associated proteins and their role in the biogenesis of small RNAs and assembly of RISC... - Tethering of human Ago proteins to mRNA mimics the miRNA-mediated repression of protein synthesisRamesh S Pillai
Friedrich Miescher Institute for Biomedical Research, P.O. Box 2543, 4002 Basel, Switzerland
RNA 10:1518-25. 2004..These findings indicate that a primary function of miRNAs is to guide their associated proteins to the mRNA... - Proteomics joins the search for microRNA targetsHelge Grosshans
Friedrich Miescher Institute for Biomedical Research, CH 4002 Basel, Switzerland
Cell 134:560-2. 2008..This approach is a powerful means to identify miRNA targets and to quantify the contribution of translational repression to posttranscriptional gene silencing by miRNAs... - The widespread regulation of microRNA biogenesis, function and decayJacek Krol
Friedrich Miescher Institute for Biomedical Research, 4002 Basel, Switzerland
Nat Rev Genet 11:597-610. 2010..Such regulation has an important role in the context-specific functions of miRNAs... - Multiple independent domains of dGW182 function in miRNA-mediated repression in DrosophilaMarina Chekulaeva
Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721, USA
RNA 15:794-803. 2009..Each of these domains also functions independently of poly(A) tails. These results indicate that miRNA-mediated repression is facilitated by multiple domains of GW182... - HuR protein attenuates miRNA-mediated repression by promoting miRISC dissociation from the target RNAPradipta Kundu
Friedrich Miescher Institute for Biomedical Research, PO Box 2543, 4002 Basel, Switzerland
Nucleic Acids Res 40:5088-100. 2012..Further, we demonstrate that HuR association with AREs can also inhibit miRNA-mediated deadenylation of mRNA in the Krebs-2 ascites extract, in a manner likewise depending on the potential of HuR to oligomerize... - Mechanisms of miRNA-mediated post-transcriptional regulation in animal cellsMarina Chekulaeva
Friedrich Miescher Institute for Biomedical Research, 4002 Basel, Switzerland
Curr Opin Cell Biol 21:452-60. 2009..In this report, we review current progress in understanding how miRNAs execute these effects in animals and we discuss some of the controversies regarding different modes of miRNA function... - Properties of the regulatory RNA-binding protein HuR and its role in controlling miRNA repressionNicole Claudia Meisner
Novartis Institutes for BioMedical Research, Novartis Campus, 4002 Basel, Switzerland
Adv Exp Med Biol 700:106-23. 2010..In this chapter we review properties of HuR and describe examples of the cross-talk between the protein and miRNAs, with emphasis on response of the regulation to cellular stress... - RNAi: the nuts and bolts of the RISC machineWitold Filipowicz
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland
Cell 122:17-20. 2005.... - Characterizing light-regulated retinal microRNAs reveals rapid turnover as a common property of neuronal microRNAsJacek Krol
Friedrich Miescher Institute for Biomedical Research, PO Box 2543, 4002 Basel, Switzerland
Cell 141:618-31. 2010..Our results demonstrate that microRNA metabolism in neurons is higher than in most other cells types and linked to neuronal activity... - dsRNA expression in the mouse elicits RNAi in oocytes and low adenosine deamination in somatic cellsJana Nejepinska
Institute of Molecular Genetics AS CR, Videnska 1083, 14220 Prague 4, Czech Republic
Nucleic Acids Res 40:399-413. 2012..RNA editing neither prevented the cytoplasmic localization nor processing into siRNAs. Thus, a long dsRNA structure is well tolerated in mammalian cells and is mainly causing a robust RNAi response in oocytes... - Lack of homologous sequence-specific DNA methylation in response to stable dsRNA expression in mouse oocytesPetr Svoboda
Friedrich Miescher Institute for Biomedical Research, PO Box 2543, 4002 Basel, Switzerland
Nucleic Acids Res 32:3601-6. 2004..These data demonstrate that dsRNA does not directly induce DNA methylation in the trans form of this sequence in these mammalian cells... - UBA1 and UBA2, two proteins that interact with UBP1, a multifunctional effector of pre-mRNA maturation in plantsMark H L Lambermon
Friedrich Miescher Institute for Biomedical Research, 4002 Basel, Switzerland
Mol Cell Biol 22:4346-57. 2002..These and other data suggest that UBP1, UBA1a, and UBA2a may act as components of a complex recognizing U-rich sequences in plant 3'-UTRs and contributing to the stabilization of mRNAs in the nucleus... - Human Dicer preferentially cleaves dsRNAs at their termini without a requirement for ATPHaidi Zhang
Friedrich Miescher Institute for Biomedical Research, PO Box 2543, CH 4002 Basel, Switzerland
EMBO J 21:5875-85. 2002..Additional experiments suggest that if ATP participates in the Dicer reaction in mammalian cells, it might be involved in product release needed for the multiple turnover of the enzyme... - Characterization of the interactions between mammalian PAZ PIWI domain proteins and DicerNasser Tahbaz
Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada
EMBO Rep 5:189-94. 2004..Lastly, we show that PPD proteins and Dicer are present in soluble and membrane-associated fractions, indicating that interactions between these two types of proteins may occur in multiple compartments... - MicroRNA inhibition of translation initiation in vitro by targeting the cap-binding complex eIF4FGeraldine Mathonnet
Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec, Canada, H3G 1Y6
Science 317:1764-7. 2007..Our results indicate that inhibition of translation initiation is the earliest molecular event effected by miRNAs. Other mechanisms, such as mRNA degradation, may subsequently consolidate mRNA silencing... - Molecular biology: the expanding world of small RNAsHelge Grosshans
Nature 451:414-6. 2008 - ATP modulates siRNA interactions with an endogenous human Dicer complexJanice L Pellino
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL 60208-3500, USA
RNA 11:1719-24. 2005..Complex D could impinge upon the RISC assembly pathway in humans, similar to an analogous complex in Drosophila... - The chromatoid body of male germ cells: similarity with processing bodies and presence of Dicer and microRNA pathway componentsNoora Kotaja
Institut de Genetique et de Biologie Moleculaire et Cellulaire, B P 10142, 67404 Illkirch Strasbourg, France
Proc Natl Acad Sci U S A 103:2647-52. 2006..Our findings underscore the importance of posttranscriptional gene regulation and of the microRNA pathway in the control of postmeiotic male germ cell differentiation... - From RNAi to epigenomes: how RNA rules the worldEric Westhof
, , , 67084 Strasbourg, France
Chembiochem 6:441-3. 2005 - Repression of protein synthesis by miRNAs: how many mechanisms?Ramesh S Pillai
European Molecular Biology Laboratory, Grenoble Outstation, B P 181, 38042 Grenoble Cedex 9, France
Trends Cell Biol 17:118-26. 2007..Recent data support different microRNA mechanisms and a role for cytoplasmic processing bodies in the degradation and storage of mRNAs targeted by microRNA regulators... - A novel microarray approach reveals new tissue-specific signatures of known and predicted mammalian microRNAsIwan Beuvink
Novartis Institutes for BioMedical Research, Genome and Proteome Sciences, Basel, Switzerland
Nucleic Acids Res 35:e52. 2007.... - Interferon signaling and treatment outcome in chronic hepatitis CMagdalena Sarasin-Filipowicz
Department of Biomedicine, University of Basel, CH 4031 Basel, Switzerland
Proc Natl Acad Sci U S A 105:7034-9. 2008.... - Crystal structures of the semireduced and inhibitor-bound forms of cyclic nucleotide phosphodiesterase from Arabidopsis thalianaAndreas Hofmann
Macromolecular Crystallography Laboratory, NCI, National Institutes of Health, Frederick, Maryland 21702, USA
J Biol Chem 277:1419-25. 2002..The ligand is bound within the active site, and the mode of binding is in agreement with the previously proposed enzymatic mechanism. Selected biophysical properties of the oxidized and the semireduced CPDase are also discussed...