DOCSLIB.ORG

Nucleus and Gene Expression Editorial Overview Elisa Izaurralde and Phillip D Zamore

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Nucleus and Gene Expression Editorial Overview Elisa Izaurralde and Phillip D Zamore Available online at www.sciencedirect.com Nucleus and gene expression Editorial overview Elisa Izaurralde and Phillip D Zamore Current Opinion in Cell Biology 2009, 21:331–334 Available online 14th May 2009 0955-0674/$ – see front matter # 2009 Elsevier Ltd. All rights reserved. DOI 10.1016/j.ceb.2009.04.013 Elisa Izaurralde That most information flows from DNA through RNA to protein remains the Department of Biochemistry, Max-Planck- organizing principle of modern molecular biology. Thus we begin this issue Institute for Developmental Biology, with an introduction to DNA replication by Mike O’Donnell and Nina Yao. Spemannstrasse 35, D-72076 Tu¨ bingen, Germany They describe the composition and function of the replisome, the machine e-mail: [email protected] that organizes activities at the replication fork, highlighting the unique challenges solved in the evolution of DNA replication proteins. Not only Elisa Izaurralde leads the does the replisome coordinate DNA copying on the leading and lagging Department of Biochemistry at the strands, it also allows the replication apparatus to skip over DNA lesions and Max Planck Institute for to pass a transcribing RNA polymerase without interrupting either tran- Developmental Biology in Tu¨ bingen, scription or replication. Germany. Her research focuses on the molecular mechanisms that Initiating transcription at the right place, at the right time, and in the right regulate gene expression at the cells is, of course, the primary challenge of gene regulation. Timothy post-transcriptional level, with Sikorski and Stephen Buratowski identify a key paradox in initiating mRNA particular emphasis on mRNA transcription: a conserved set of transcription initiation proteins are used to surveillance, decay, and silencing in recruit a common RNA polymerase, RNA Pol II, to many different tran- scription initiation sequences (promoters). They describe our current un- animal cells. derstanding of how eukaryotes solve this problem, describing the Phillip D Zamore experimental support for distinct initiation pathways for different promoter types. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, Not all transcription is productive. Synthesis in yeast of seemingly futile United States cryptic unstable transcripts (CUTs), which are copied from intergenic DNA, e-mail: [email protected] underscores the truism that eukaryotic solutions to biological problems are often wasteful. CUTs are typically marked for destruction while still in the Phillip D Zamore is an investigator nucleus, where they are degraded by the nuclear exosome complex [1,2]. of the Howard Hughes Medical The late Dmitry Belostotsky reviews the function and mechanism of the Institute and the Gretchen Stone nuclear and cytoplasmic exosomes, complex assemblies of ribonucleases and Cook Professor of Biomedical other proteins that control RNA stability, participate in 30-end processing of Science in the Department of structured RNAs and in post-transcriptional gene silencing, as well as Biochemistry and Molecular provide quality control for RNA processing, folding, and RNP assembly. Pharmacology at the University of Belostotsky also reviews the growing number of noncoding transcript classes Massachusetts Medical School in whose RNAs are widely distributed across the genome, yet whose abun- Worcester, MA, USA. His laboratory dance suggests that like CUTs, they are degraded nearly as rapidly as they studies how small RNAs guide are made. silencing of gene expression in plants, fungi, and animals and how At the opposite end of the continuum of RNA stability lie highly stable, these RNA silencing pathways can structural RNAs, many of which regulate transcription globally or locally. be used to design novel therapies Among the most intensively studied are xist and its complementary counter- for human disease. part tsix. Jennifer Chow and Edith Heard describe how xist, tsix, and a host of protein factors act sequentially to silence one of the two X chromosomes in mammals. As females have twice as many X chromosomes as males, such X chromosome inactivation serves to equalize the expression of X-linked www.sciencedirect.com Current Opinion in Cell Biology 2009, 21:331–334 332 Nucleus and gene expression genes between the sexes. (In flies, an unrelated structural a housekeeping gene required for snRNP assembly. RNA, roX, acts to upregulate the single X chromosome in snRNAs participate in pre-mRNA splicing as protein– males, allowing its single-copy X-linked genes to catch up RNA complexes whose production requires a remarkable with the corresponding two copies of each gene in number of assembly proteins. Utz Fischer describes our females [3].) The study of X inactivation in mammals current understanding of how SMN protein, as a com- promises to inform our understanding of the more general ponent of the multiprotein SMN complex, acts to facili- problem of mono-allelic gene expression, whose role in tate the assembly of Sm proteins onto the U snRNAs in titrating mRNA production to appropriate levels remains the cytoplasm. The final step in snRNP assembly is the poorly understood. conversion of the 7-monomethyl guanosine cap of the U snRNA into a 2,2,7-trimethyl guanosine cap, permitting Most of the genome is transcribed in eukaryotes — per- its reimportation into the nucleus, where it can participate haps 90% in humans — although just a small percentage in pre-mRNA splicing. The devastating phenotype of encodes proteins. Some of these noncoding transcripts spinal muscular atrophy, thought to reflect the disruption pair to form double-stranded RNA (dsRNA) or are copied of splicing patterns of a subset of mRNAs particularly into dsRNA by RNA-dependent RNA polymerases. Such important for neurons, underscores the importance of dsRNA can be the source of endogenous small interfering snRNP assembly. RNAs (endo-siRNAs) that silence protein-coding genes in trans. In plants, a specialized DNA-dependent RNA Errors in pre-mRNA splicing often produce mRNAs with polymerase, RNA Pol IV, transcribes endo-siRNA-gen- diminished coding potential. When these aberrant tran- erating loci involved in RNA-directed DNA methylation. scripts contain premature stop codons, a specialized qual- Marjorie Matzke and colleagues review our current un- ity control mechanism, the nonsense-mediated decay derstanding of the mechanism, genetics, and biological (NMD) pathway, ensures their destruction before they function of RNA-directed DNA methylation. They can produce aberrant, potentially toxic, protein. Indrani describe our current understanding of how plant RNA Rebbapragada and Jens Lykke-Andersen evaluate the polymerases specialized to transcribe ‘silent’ chromatin evidence supporting prominent explanations for how participate in siRNA production and how such endo- the NMD pathway distinguishes between premature siRNAs, in turn, act on chromatin and DNA. They and appropriate stop codons. One intriguing model is remind us that most RNA-guided silencing mechanisms that premature stop codons reside in regions of the in plants later found parallels in animals, so a thorough mRNA bearing a distinct complement of RNA-binding understanding of the RNA Pol IV mechanism may ulti- proteins deposited during nuclear pre-mRNA splicing, mately lead us to its animal analog. but sensed in the cytoplasm during a ‘pioneer round’ of translation — that is, the initial transit of the mRNA by a In most eukaryotes, the primary transcripts of nearly all ribosome. protein-coding genes are mainly intervening sequence (introns), punctuated by coding segments (exons). The Roy Parker and colleagues continue the theme of RNA pre-mRNA splicing pathway removes introns and joins degradation. They explain that high rates of translational exons from such pre-mRNA transcripts, thus assembling a initiation and mRNA turnover are inversely related: functional mRNA appropriate for export to the cyto- proteins that promote translational initiation discourage plasm. Correctly identifying splice sites is essential to mRNA destruction, whereas proteins that bind the this process. Both splice site identification and the sub- mRNA cap but do not recruit translational initiation sequent breaking and joining of phosphodiester bonds factors, as well as proteins that promote decapping, requires the spliceosomal small nuclear RNAs (snRNAs) repress protein synthesis, and redirect the mRNA to U1, U2, U4, U5, and U6, or their equivalents in the specialized RNA–protein granules called processing or ‘minor’ spliceosome. Beyond simply removing introns, P bodies. Here, mRNAs can be degraded or stored for pre-mRNA splicing expands the genic repertoire of later re-entry into the actively translated pool. mRNAs eukaryotes by allowing a single gene to encode alterna- stalled in the process of translation also accumulate in tive forms of a single protein or alternative mRNA regu- stress granules. The movements of mRNAs among poly- latory sequences or both. Such alternative splicing is somes, P bodies, and stress granules are poorly under- thought to occur in most human genes. Britta Hartman stood. Moreover, as Parker and colleagues note, we do not and Juan Valca´rcel summarize our current understanding yet understand why mRNAs that have exited the poly- of how successful alternative splicing expands the num- some pool should accumulate in granules, since cells ber of functions encoded by our genes and how failures of unable to form such structures can
Load more

Recommended publications
  • EMBC Annual Report 2007
    EMBO | EMBC annual report 2007 EUROPEAN MOLECULAR BIOLOGY ORGANIZATION | EUROPEAN MOLECULAR BIOLOGY CONFERENCE EMBO | EMBC table of contents introduction preface by Hermann Bujard, EMBO 4 preface by Tim Hunt and Christiane Nüsslein-Volhard, EMBO Council 6 preface by Marja Makarow and Isabella Beretta, EMBC 7 past & present timeline 10 brief history 11 EMBO | EMBC | EMBL aims 12 EMBO actions 2007 15 EMBC actions 2007 17 EMBO & EMBC programmes and activities fellowship programme 20 courses & workshops programme 21 young investigator programme 22 installation grants 23 science & society programme 24 electronic information programme 25 EMBO activities The EMBO Journal 28 EMBO reports 29 Molecular Systems Biology 30 journal subject categories 31 national science reviews 32 women in science 33 gold medal 34 award for communication in the life sciences 35 plenary lectures 36 communications 37 European Life Sciences Forum (ELSF) 38 ➔ 2 table of contents appendix EMBC delegates and advisers 42 EMBC scale of contributions 49 EMBO council members 2007 50 EMBO committee members & auditors 2007 51 EMBO council members 2008 52 EMBO committee members & auditors 2008 53 EMBO members elected in 2007 54 advisory editorial boards & senior editors 2007 64 long-term fellowship awards 2007 66 long-term fellowships: statistics 82 long-term fellowships 2007: geographical distribution 84 short-term fellowship awards 2007 86 short-term fellowships: statistics 104 short-term fellowships 2007: geographical distribution 106 young investigators 2007 108 installation
    [Show full text]
  • Dissertation
    Regulation of gene silencing: From microRNA biogenesis to post-translational modifications of TNRC6 complexes DISSERTATION zur Erlangung des DOKTORGRADES DER NATURWISSENSCHAFTEN (Dr. rer. nat.) der Fakultät Biologie und Vorklinische Medizin der Universität Regensburg vorgelegt von Johannes Danner aus Eggenfelden im Jahr 2017 Das Promotionsgesuch wurde eingereicht am: 12.09.2017 Die Arbeit wurde angeleitet von: Prof. Dr. Gunter Meister Johannes Danner Summary ‘From microRNA biogenesis to post-translational modifications of TNRC6 complexes’ summarizes the two main projects, beginning with the influence of specific RNA binding proteins on miRNA biogenesis processes. The fate of the mature miRNA is determined by the incorporation into Argonaute proteins followed by a complex formation with TNRC6 proteins as core molecules of gene silencing complexes. miRNAs are transcribed as stem-loop structured primary transcripts (pri-miRNA) by Pol II. The further nuclear processing is carried out by the microprocessor complex containing the RNase III enzyme Drosha, which cleaves the pri-miRNA to precursor-miRNA (pre-miRNA). After Exportin-5 mediated transport of the pre-miRNA to the cytoplasm, the RNase III enzyme Dicer cleaves off the terminal loop resulting in a 21-24 nt long double-stranded RNA. One of the strands is incorporated in the RNA-induced silencing complex (RISC), where it directly interacts with a member of the Argonaute protein family. The miRNA guides the mature RISC complex to partially complementary target sites on mRNAs leading to gene silencing. During this process TNRC6 proteins interact with Argonaute and recruit additional factors to mediate translational repression and target mRNA destabilization through deadenylation and decapping leading to mRNA decay.
    [Show full text]
  • The GW182 Protein Family in Animal Cells: New Insights Into Domains Required for Mirna-Mediated Gene Silencing
    Downloaded from rnajournal.cshlp.org on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW The GW182 protein family in animal cells: New insights into domains required for miRNA-mediated gene silencing ANA EULALIO, FELIX TRITSCHLER, and ELISA IZAURRALDE Department of Biochemistry, Max Planck Institute for Developmental Biology, D-72076 Tu¨bingen, Germany ABSTRACT GW182 family proteins interact directly with Argonaute proteins and are required for miRNA-mediated gene silencing in animal cells. The domains of the GW182 proteins have recently been studied to determine their role in silencing. These studies revealed that the middle and C-terminal regions function as an autonomous domain with a repressive function that is independent of both the interaction with Argonaute proteins and of P-body localization. Such findings reinforce the idea that GW182 proteins are key components of miRNA repressor complexes in metazoa. Keywords: Argonaute; GW182; miRNAs; mRNA decay; P-bodies; RBD; RRM; TNRC6A INTRODUCTION are conserved in diverse organisms (for review, see Carthew and Sontheimer 2009; Kim et al. 2009). Among proteins MicroRNAs are genome-encoded small RNAs that post- that play a general role, those in the GW182 family have transcriptionally regulate gene expression and play critical emerged as key components of miRNA repressive com- roles in a wide range of important biological processes plexes in animal cells (for review, see Ding and Han 2007; including cell growth, division and differentiation, and Eulalio et al. 2007a, 2008a). organism metabolism and development. About 500–1000 The precise molecular function of GW182 proteins in the miRNA genes exist in vertebrates and plants, and 100 in miRNA pathway is not fully understood; yet, recent studies invertebrates, and each miRNA is predicted to have target have provided new insights into their role in silencing sites in hundreds of mRNAs, suggesting that miRNAs (Chekulaeva et al.
    [Show full text]
  • Program Information
    RNA 2021 The 26th Annual Meeting of the RNA Society On-line May 25–June 4, 2021 RNA 2021 On-Line The 26th Annual Meeting of the RNA Society CORRECT THE MESSAGE CHANGE A LIFETM Locanabio’s CORRECTXTM platform is pioneering a new class of gene therapies by correcting the th th May 25 – June 4 , 2021 dysfunctional RNA that causes a broad range of neurodegenerative, neuromuscular and retinal diseases Gene Yeo – University of California San Diego, USA Katrin Karbstein – Scripps Research Institute, Florida, USA V. Narry Kim – Seoul National University, South Korea Anna Marie Pyle – Yale University, USA Xavier Roca – Nanyang Technological University, Singapore Jörg Vogel – University of Würzburg, Germany RNA 2021 • On-line GENERAL INFORMATION Citation of abstracts presented during RNA 2021 On-line (in bibliographies or other) is strictly prohibited. Material should be treated as personal communication and is to be cited only with the expressed written ® consent of the author(s). The Sequel IIe System NO UNAUTHORIZED PHOTOGRAPHY OF ANY MATTER PRESENTED DURING THE ON-LINE MEETING: To encourage sharing of unpublished data at the RNA Society Annual Meeting, taking of photographs, screenshots, videos, and/or downloading or saving Reveal the functional e ects any material is strictly prohibited. of alternative splicing with USE OF SOCIAL MEDIA: The official hash tag of the 26th Annual Meeting of the RNA Society is full-length transcript sequencing #RNA2021. The organizers encourage attendees to tweet about the amazing science they experience during the meeting. However, please respect these few simple rules when using the #RNA2021 hash tag, or when talking about the meeting on Twitter and other social media platforms: 1.
    [Show full text]
  • The Myth of Junk DNA
    The Myth of Junk DNA JoATN h A N W ells s eattle Discovery Institute Press 2011 Description According to a number of leading proponents of Darwin’s theory, “junk DNA”—the non-protein coding portion of DNA—provides decisive evidence for Darwinian evolution and against intelligent design, since an intelligent designer would presumably not have filled our genome with so much garbage. But in this provocative book, biologist Jonathan Wells exposes the claim that most of the genome is little more than junk as an anti-scientific myth that ignores the evidence, impedes research, and is based more on theological speculation than good science. Copyright Notice Copyright © 2011 by Jonathan Wells. All Rights Reserved. Publisher’s Note This book is part of a series published by the Center for Science & Culture at Discovery Institute in Seattle. Previous books include The Deniable Darwin by David Berlinski, In the Beginning and Other Essays on Intelligent Design by Granville Sewell, God and Evolution: Protestants, Catholics, and Jews Explore Darwin’s Challenge to Faith, edited by Jay Richards, and Darwin’s Conservatives: The Misguided Questby John G. West. Library Cataloging Data The Myth of Junk DNA by Jonathan Wells (1942– ) Illustrations by Ray Braun 174 pages, 6 x 9 x 0.4 inches & 0.6 lb, 229 x 152 x 10 mm. & 0.26 kg Library of Congress Control Number: 2011925471 BISAC: SCI029000 SCIENCE / Life Sciences / Genetics & Genomics BISAC: SCI027000 SCIENCE / Life Sciences / Evolution ISBN-13: 978-1-9365990-0-4 (paperback) Publisher Information Discovery Institute Press, 208 Columbia Street, Seattle, WA 98104 Internet: http://www.discoveryinstitutepress.com/ Published in the United States of America on acid-free paper.
    [Show full text]
  • P-Body Formation Is a Consequence, Not the Cause, of RNA-Mediated Gene Silencing Ana Eulalio, Isabelle Behm-Ansmant, Daniel Schweizer, Elisa Izaurralde
    P-Body Formation Is a Consequence, Not the Cause, of RNA-Mediated Gene Silencing Ana Eulalio, Isabelle Behm-Ansmant, Daniel Schweizer, Elisa Izaurralde To cite this version: Ana Eulalio, Isabelle Behm-Ansmant, Daniel Schweizer, Elisa Izaurralde. P-Body Formation Is a Consequence, Not the Cause, of RNA-Mediated Gene Silencing. Molecular and Cellular Biology, American Society for Microbiology, 2007, 27 (11), pp.3970-3981. 10.1128/MCB.00128-07. hal- 01738446 HAL Id: hal-01738446 https://hal.archives-ouvertes.fr/hal-01738446 Submitted on 20 Mar 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. MOLECULAR AND CELLULAR BIOLOGY, June 2007, p. 3970–3981 Vol. 27, No. 11 0270-7306/07/$08.00ϩ0 doi:10.1128/MCB.00128-07 Copyright © 2007, American Society for Microbiology. All Rights Reserved. P-Body Formation Is a Consequence, Not the Cause, of RNA-Mediated Gene Silencingᰔ† Ana Eulalio, Isabelle Behm-Ansmant, Daniel Schweizer, and Elisa Izaurralde* MPI for Developmental Biology, Spemannstrasse 35, D-72076 Tu¨bingen, Germany Received 19 January 2007/Returned for modification 16 February 2007/Accepted 19 March 2007 P bodies are cytoplasmic domains that contain proteins involved in diverse posttranscriptional processes, such as mRNA degradation, nonsense-mediated mRNA decay (NMD), translational repression, and RNA- mediated gene silencing.
    [Show full text]
  • Wednesday 09 October 2013 14:00 - 16:45 Arrival and Registration ATC Foyer
    Programme Wednesday 09 October 2013 14:00 - 16:45 Arrival and registration ATC Foyer 16:45 - 17:00 Welcome ATC Auditorium 17:00 - 20:15 Session 1: The diversity of non-coding RNAs Chair: Elisa Izaurralde ATC Auditorium 17:00 - 17:30 Central roles of bacterial RNAs in regulating 1 metabolism Gisela Storz NICHD, NIH, United States of America 17:30 - 18:00 RNA: protein interactions 2 Nikolaus Rajewsky Max Delbrück Center for Molecular Medicine, Germany 18:00 - 18:15 Natural RNA circles function as efficient miRNA 3 sponges Thomas Hansen Aarhus University, Denmark 18:15 - 18:45 Coffee Break ATC Foyer 18:45 - 19:15 The human genome as the zip file extraordinaire 4 John Mattick Garvan Institute of Medical Research, Australia 19:15 - 19:45 RNA silencing and epigenetics in plants 5 David Baulcombe University of Cambridge, United Kingdom 19:45 - 20:00 Cross-talking noncoding RNAs confer central 6 nervous system specificity to Spinocerebellar Ataxia 7 pathology Ana Marques University of Oxford, United Kingdom EMBO|EMBL Symposium The Non-Coding Genome 20:00 - 20:15 A long non coding RNA regulates chromatin mediated 7 modulation of alternative splicing Reini Luco IGH-CNRS, France 20:15 - 23:00 Dinner Canteen Page 6 Programme Thursday 10 October 2013 09:00 - 12:15 Session 2: miRNA function and mechanisms Chair: David P. Bartel ATC Auditorium 09:00 - 09:30 The roles of long noncoding RNA in epigenetic 8 regulation Jeannie Lee Massachusetts General Hospital, United States of America 09:30 - 10:00 3’ end modifications in the MicroRNA pathway 9 V.
    [Show full text]
  • Nuclear Export of Different Classes of RNA Is Mediated by Specific Factors Artur Jarmolowski, Wilbert C
    Nuclear Export of Different Classes of RNA Is Mediated by Specific Factors Artur Jarmolowski, Wilbert C. Boelens, Elisa Izaurralde, and Iain W. Mattaj European Molecular Biology Laboratory, 69117 Heidelberg, Germany Abstract. Various classes of RNA are exported from tions at which they have no effect on the export of het- the nucleus to the cytoplasm, including transcripts of erologous RNAs. While the export of both U snRNAs RNA polymerase I (large ribosomal RNAs), II (U-rich and mRNAs is enhanced by their 7-methyl guanosine small nuclear RNAs [U snRNAs], mRNAs), and III cap structures, factors recognizing this structure are (tRNAs, 5S RNA). Here, evidence is presented that found to be limiting in concentration only in the case some steps in the export of various classes of nuclear of U snRNAs. In addition to the specific factors, evi- RNA are mediated by specific rather than common dence for steps in the export process that may be com- factors. Using microinjection into Xenopus oocytes, it mon to at least some classes of RNA are provided by is shown that a tRNA, a U snRNA, and an mRNA experiments in which synthetic homopolymeric RNAs competitively inhibit their own export at concentra- are used as inhibitors. ALYSIS of the mechanisms of transport of macro- ribosomal protein 1.5, implicating these proteins as media- molecules from the cytoplasm to the nucleus is a tors of 5S export (Guddat et al., 1990). In the case of the field of very active study (reviewed by Garcia-Bustos tRNA mutants, a correlation between export and ability to et al., 1991; Silver, 1991; Dingwall and Laskey, 1992; Ger- hind to the metabolic enzyme glyceraldehyde-3-phosphate ace, 1992; Newmeyer, 1993).
    [Show full text]
  • EMBO Facts & Figures 2010
    promoting excellence in the molecular life sciences promoting excellence in the molecular life sciences gators|courses,workshops,conference series & symposia|installation grantees|long-term fellows|short-term fellows|policy, science & society|the EMBO Journal|EMBO reports|molecular systems biology|EMBO molecular medicine|global exchange|gold medal|the EMB molecular systems biology|EMBO molecular medicine|global exchange|gold medal|the EMBO meeting|women in science|young investigators|courses,workshops,conference series & symposia|installation grantees|long-term fellows|short-term fellows|policy, science nge|gold medal|the EMBO meeting|women in science|young investigators|long-term fellows|short-term fellows|policy, science & society|the EMBO Journal|courses,workshops,conference series & symposia|EMBO reports|molecular systems biology|EMBO molecular medi ar medicine|installation grantees|long-term fellows|gold medal|molecular systems biology|short-term fellows|the EMBO meeting|women in science|youngReykjavik investigators|courses,workshops,conference series & symposia|global exchange|EMBO reports|policy, science e EMBO meeting|women in science|young investigators|courses,workshops,conference series & symposia|global exchange|policy, science & society|the EMBO Journal|EMBO reports|molecular systems biology|EMBO molecular medicine|installation grantees|long-term shops,conference series & symposia|global exchange|EMBO reports|gold medal|installation grantees|the EMBO Journal|the EMBO meeting|women in science|young investigators|long-term
    [Show full text]
  • A Crucial Role for GW182 and the DCP1:DCP2 Decapping Complex in Mirna-Mediated Gene Silencing
    Downloaded from rnajournal.cshlp.org on October 3, 2021 - Published by Cold Spring Harbor Laboratory Press A crucial role for GW182 and the DCP1:DCP2 decapping complex in miRNA-mediated gene silencing JAN REHWINKEL, ISABELLE BEHM-ANSMANT, DAVID GATFIELD, and ELISA IZAURRALDE European Molecular Biology Laboratory (EMBL), D-69117 Heidelberg, Germany ABSTRACT In eukaryotic cells degradation of bulk mRNA in the 50 to 30 direction requires the consecutive action of the decapping complex (consisting of DCP1 and DCP2) and the 50 to 30 exonuclease XRN1. These enzymes are found in discrete cytoplasmic foci known as P-bodies or GW-bodies (because of the accumulation of the GW182 antigen). Proteins acting in other post-transcriptional processes have also been localized to P-bodies. These include SMG5, SMG7, and UPF1, which function in nonsense-mediated mRNA decay (NMD), and the Argonaute proteins that are essential for RNA interference (RNAi) and the micro-RNA (miRNA) pathway. In addition, XRN1 is required for degradation of mRNAs targeted by NMD and RNAi. To investigate a possible interplay between P-bodies and these post-transcriptional processes we depleted P-body or essential pathway components from Drosophila cells and analyzed the effects of these depletions on the expression of reporter constructs, allowing us to monitor specifically NMD, RNAi, or miRNA function. We show that the RNA-binding protein GW182 and the DCP1:DCP2 decapping complex are required for miRNA-mediated gene silencing, uncovering a crucial role for P-body components in the miRNA pathway. Our analysis also revealed that inhibition of one pathway by depletion of its key effectors does not prevent the functioning of the other pathways, suggesting a lack of interdependence in Drosophila.
    [Show full text]
  • Annual Report 20
    80045• HFSP-RA-2011-couv_couv2012 04/06/12 16:44 Page1 11 Acknowledgements HFSPO is grateful for the support of: Australia National Health and Medical Research Council (NHMRC) Canada Canadian Institute of Health Research (CIHR) Natural Sciences and Engineering Research Council (NSERC) European Union European Commission - Directorate General Information Society (DG INFSO) 20 REPORT ANNUAL European Commission - Directorate General Research (DG RESEARCH) France Communauté Urbaine de Strasbourg (CUS) Ministère de l’Enseignement Supérieur et de la Recherche (MESR) Région Alsace Germany Federal Ministry of Education and Research (BMBF) India Department of Biotechnology (DBT) Ministry of Science and Technology Italy Ministry of Education, University and Research Japan Ministry for Economy, Trade and Industry (METI) Ministry of Education, Culture, Sports, Science and Technology (MEXT) Republic of Korea Ministry of Education, Science and Technology (MEST) New Zealand Health Research Council (HRC) Norway Research Council of Norway (RCN) Switzerland State Secretariat for Education and Research (SER) United Kingdom Biotechnology and Biological Sciences Research Council (BBSRC) Medical Research Council (MRC) The International Human Frontier Science United States of America Program Organization (HFSPO) National Institutes of Health (NIH) 12 quai Saint Jean - BP 10034 National Science Foundation (NSF) 67080 Strasbourg CEDEX - France Fax. +33 (0)3 88 32 88 97 e-mail: [email protected] Web site: www.hfsp.org Japanese web site: http://jhfsp.jsf.or.jp 80045• HFSP-RA-2011-couv_couv2012 04/06/12 16:44 Page2 HUMAN FRONTIER SCIENCE PROGRAM The Human Frontier Science Program is unique, supporting international collaboration to undertake innovative, risky, basic research at the frontier of the life sciences.
    [Show full text]
  • Celebrating Meet the 56 New EMBO Members Gold Medal Awarded To
    SUMMER 2019 ISSUE 42 Scientists from 22 countries elected Meet the 56 new EMBO Members PAGES 6-7 Celebrating Five decades of funding Symposium M. Madan Babu and Paola Picotti honoured marks EMBC Gold Medal awarded to anniversary two systems biologists PAGES 10 – 13 PAGE 3 Member mentors Young Investigator Plan S implementation Life Science Alliance Three mentoring pairs share their stories EMBO responds to publication Spotlight on the newest journal of updated guidance PAGES 8 – 9 PAGE 14 PAGE 16 www.embo.org TABLE OF CONTENTS EMBO NEWS EMBO news Science policy Meet the EMBO Gold Medal recipients EMBO responds to updated Plan S guidance Page 3 Page 14 Gold Medal interview with Madan Babu Roundup from the World Conference on Page 4 Research Integrity EMBL Photolab Marietta Schupp, © Page 14 Gold Medal interview with Paola Picotti Editorial Pages 5 EMBO community or those of us who know EMBO in the 56 new EMBO Members elected present day – a respected organization Pages 6 –­ 7 Fwith more than 1800 members, stable funding and strong connections throughout Europe and the world – it is easy to forget that in the early days EMBO’s financial future was far from secure. After a grant from the Volkswagen Stiftung funded the EMBO Fellowships for the first EMBL Photolab Marietta Schupp. © five years, stable and, importantly, inde- pendent funding was only achieved when EMBO’s intergovernmental funding body, Updates from across Europe the European Molecular Biology Conference Two systems biologists receive EMBO Gold Medal (EMBC) was established in 1969. Pages 17 –­ 19 Twelve European countries initially signed Award recognizes the work of M.
    [Show full text]