DOCSLIB.ORG

THÈSE Présentée Par : Semih CETIN

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
THÈSE Présentée Par : Semih CETIN UNIVERSITÉ DE STRASBOURG ÉCOLE DOCTORALE DES SCIENCES DE LA VIE ET DE LA SANTÉ UPR 9002 THÈSE présentée par : Semih CETIN soutenue le : 12 septembre 2016 pour obtenir le grade de : Docteur de l’université de Strasbourg Discipline / Spécialité : Sciences du vivant / Aspects moléculaire et cellulaire de la biologie Caractérisation moléculaire du mécanisme de dégradation des microARN par un transcrit cible THÈSE dirigée par : Mr PFEFFER Sébastien Directeur de recherche CNRS, Université de Strasbourg RAPPORTEURS : Mr BRODERSEN Peter Associate Professor, Université de Copenhague Mme VANACOVA Stěpánka Associate Professor, Université de Masaryk AUTRES MEMBRES DU JURY : Mr GAGLIARDI Dominique Directeur de recherche CNRS, Université de Strasbourg Mr FILIPOWICZ Witold Professeur, Friedrich Miescher Institute for Biomedical Research Acknowledgements I would like to first of all thank Sébastien for giving me the opportunity to do my thesis in his laboratory. I am very grateful to have been a part of his team, the members of which he chooses so well to form a very diverse and interesting bunch that creates a very enjoyable learning and growing environment. Thank you for being so supportive and always accessible to talk science or any other subject. Being supervised by Sebastien was very enriching experience for which I will forever be grateful, rich in learning and experiences not only through my main work in the lab but also through the collaborations he allowed me to take part in as well as the teaching missions that he encouraged me to pursue at the faculty. I would also like to thank the members of the jury, Peter Brodersen, Stěpánka Vanacova and Dominique Gagliardi for accepting to judge my work and for their invaluable feedback through the very interesting and stressful scientific discussion during my defence. I would like to thank Joern Pütz for inspiring me to follow my scientific adventure in Strasbourg after my year as an Erasmus student, and for helping and supporting me tremendously along the way. I would like to thank all the former and present members of the Pfeffer laboratory; Gabrielle, Mélanie, Erika, Aurélie, Maud, Béatrice, Ramy, Diane, Guillaume, Lee, Ali, Ilyass, Mathieu, Antoine and Olivier, with whom we shared a great deal of time inside and outside of the laboratory. Thank you all for your support during these years and helping me grow personally and professionally. You have made this adventure very enjoyable and very memorable and I feel very lucky and grateful to have shared my time with you all. I am thankful to my family who have always been there for me and supported me in every way since the start, never failing to encourage me along the way. Finally, I would like to thank my girlfriend Nevcin, for being ever present, through our adventures from our Erasmus year abroad to our thesis studies. She has been the source of tremendous support during these times and the invaluable constant in my life. ii ii TABLE OF CONTENTS INTRODUCTION .............................................................................. 1 1. Biogenesis of miRNAs .......................................................................................................... 1 1.1 Canonical biogenesis of mammalian miRNA ..................................................................... 1 1.1.1 Generation of miRNA precursor and export into the cytoplasm ............................................... 1 1.1.2 Dicing of the pre-miRNA into miRNA/miRNA* duplex ............................................................... 5 1.2 Non canonical biogenesis of miRNA .................................................................................. 6 1.3 Formation of functional miRISC ......................................................................................... 8 2. Mode of action and Function of miRNAs ........................................................................... 10 2.1 Target recognition of miRNAs ......................................................................................... 10 2.2 Influence of target site context ....................................................................................... 11 2.3 Mechanism of action of miRNAs ..................................................................................... 12 2.4 Function of miRNAs ......................................................................................................... 15 3. Regulation of miRNA expression ....................................................................................... 16 3.1 Regulation of miRNA biogenesis ..................................................................................... 16 3.1.1 Transcriptional regulation ........................................................................................................ 16 3.1.2 Regulation of miRNA processing .............................................................................................. 17 3.1.2.1 Regulation of the Microprocessor .................................................................................. 17 3.1.2.2 Export regulation ............................................................................................................ 19 3.1.2.3 Regulation of Dicer processing ....................................................................................... 20 3.2 Regulation of RISC action ................................................................................................ 21 3.2.1 Regulation at the level of Argonaute proteins ......................................................................... 21 3.2.2 Regulation of the activity of Argonaute proteins by RNA binding proteins ............................. 22 4. RNA intrinsic regulation affecting miRNA expression and targeting ................................... 24 4.1 Modifications on miRNA precursor seQuences affecting their biogenesis and/or the targeting of miRNAs ..................................................................................................................... 25 4.1.1 Nucleobase substitutions on miRNA precursors ...................................................................... 25 4.1.2 Regulation of let-7 biogenesis by non-templated nucleotide additions .................................. 26 4.2 Sequence modifications on mature miRNA (isomiRs) ..................................................... 28 4.2.1 5’ isomiRs: shift in Drosha and/or Dicer cleavage .................................................................... 28 4.2.2 3’ IsomiRs: 3’ heterogeneity ..................................................................................................... 29 4.2.2.1 Exoribonucleases creating 3’ isomiRs ............................................................................. 29 4.2.2.2 Non-templated nucleotide additions on mature miRNA by mammalian terminal uridylyl transferases (TUTases) ....................................................................................................................... 30 4.2.2.3 Mammalian TUTase family and their function ................................................................ 30 5. Mature miRNA turnover ................................................................................................... 33 i 5.1 Trans acting factor in miRNA turnover ............................................................................ 34 5.1.1 miRNA turnover in plants ......................................................................................................... 34 5.1.2 miRNA turnover in Chlamydomonas reinhardtii ...................................................................... 35 5.1.3 miRNA turnover in Caenorhabditis elegans ............................................................................. 35 5.1.4 miRNA turnover in mammals ................................................................................................... 35 5.2 RNA-mediated miRNA turnover ...................................................................................... 37 5.2.1 Target-mediated miRNA protection (TMMP) ........................................................................... 38 5.2.2 Target RNA-mediated miRNA degradation .............................................................................. 38 5.2.3 miRNA degradation and viral infections ................................................................................... 40 RESULTS .......................................................................................... 44 1. Discovery of factors involved in Target RNA mediated miRNA degradation (TDMD) .......... 44 2. Identification of Argonaute 2 partners by proximity dependent labeling ........................... 48 2.1 Aim .................................................................................................................................. 48 2.2 Large scale protein interaction mapping techniQues ...................................................... 48 2.2.1 Affinity purification coupled to mass spectrometry ................................................................. 49 2.2.2 Tandem Affinity Purification ..................................................................................................... 49 2.2.3 Yeast two-hybrid system .......................................................................................................... 50 2.2.4 Proximity labelling strategies ................................................................................................... 50 2.2.4.1 APEX approach ...............................................................................................................
Load more

Recommended publications
  • The Role of Polyadenylation in the Induction of Inflammatory Genes
    The role of polyadenylation in the induction of inflammatory genes Raj Gandhi BSc & ARCS Thesis submitted for the degree of Doctor of Philosophy September 2016 Declaration Except where acknowledged in the text, I declare that this thesis is my own work and is based on research that was undertaken by me in the School of Pharmacy, Faculty of Science, The University of Nottingham. i Acknowledgements First and foremost, I give thanks to my primary supervisor Dr. Cornelia de Moor. She supported me at every step, always made time for me whenever I needed it, and was sympathetic during times of difficulty. I feel very, very fortunate to have been her student. I would also like to thank Dr. Catherine Jopling for her advice and Dr. Graeme Thorn for being so patient and giving me so much help in understanding the bioinformatics parts of my project. I am grateful to Dr. Anna Piccinini and Dr. Sadaf Ashraf for filling in huge gaps in my knowledge about inflammation and osteoarthritis, and to Dr. Sunir Malla for help with the TAIL-seq work. I thank Dr. Richa Singhania and Kathryn Williams for proofreading. Dr. Hannah Parker was my “big sister” in the lab from my first day, and I am very grateful for all her help and for her friendship. My project was made all the more enjoyable/bearable by the members of the Gene Regulation and RNA Biology group, especially Jialiang Lin, Kathryn Williams, Dr. Richa Singhania, Aimée Parsons, Dan Smalley, and Hibah Al-Masmoum. Barbara Rampersad was a wonderful technician. Mike Thomas, James Williamson, Will Hawley, Tom Upton, and Jamie Ware were some of the best of friends I could have hoped to make in Nottingham.
    [Show full text]
  • Non-Coding Rnas: Strategy for Viruses' Offensive
    non-coding RNA Review Non-Coding RNAs: Strategy for Viruses’ Offensive Alessia Gallo 1,*, Matteo Bulati 1, Vitale Miceli 1 , Nicola Amodio 2 and Pier Giulio Conaldi 1,3 1 Department of Research, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Via E.Tricomi 5, 90127 Palermo, Italy; [email protected] (M.B.); [email protected] (V.M.); [email protected] (P.G.C.) 2 Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy; [email protected] 3 UPMC Italy (University of Pittsburgh Medical Center Italy), Discesa dei Giudici 4, 90133 Palermo, Italy * Correspondence: [email protected]; Tel.: +39-91-21-92-649 Received: 7 August 2020; Accepted: 8 September 2020; Published: 10 September 2020 Abstract: The awareness of viruses as a constant threat for human public health is a matter of fact and in this resides the need of understanding the mechanisms they use to trick the host. Viral non-coding RNAs are gaining much value and interest for the potential impact played in host gene regulation, acting as fine tuners of host cellular defense mechanisms. The implicit importance of v-ncRNAs resides first in the limited genomes size of viruses carrying only strictly necessary genomic sequences. The other crucial and appealing characteristic of v-ncRNAs is the non-immunogenicity, making them the perfect expedient to be used in the never-ending virus-host war. In this review, we wish to examine how DNA and RNA viruses have evolved a common strategy and which the crucial host pathways are targeted through v-ncRNAs in order to grant and facilitate their life cycle.
    [Show full text]
  • The Chloroplast Epitranscriptome: Factors, Sites, Regulation, and Detection Methods
    G C A T T A C G G C A T genes Review The Chloroplast Epitranscriptome: Factors, Sites, Regulation, and Detection Methods Nikolay Manavski 1,† , Alexandre Vicente 1,†, Wei Chi 2 and Jörg Meurer 1,* 1 Plant Molecular Biology, Faculty of Biology, Ludwig-Maximilians-University Munich, Großhaderner Street 2-4, 82152 Planegg-Martinsried, Germany; [email protected] (N.M.); [email protected] (A.V.) 2 Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences, Beijing 100093, China; [email protected] * Correspondence: [email protected]; Tel.: +49-89-218074556 † Both authors contributed equally to this work. Abstract: Modifications in nucleic acids are present in all three domains of life. More than 170 dis- tinct chemical modifications have been reported in cellular RNAs to date. Collectively termed as epitranscriptome, these RNA modifications are often dynamic and involve distinct regulatory pro- teins that install, remove, and interpret these marks in a site-specific manner. Covalent nucleotide modifications-such as methylations at diverse positions in the bases, polyuridylation, and pseu- douridylation and many others impact various events in the lifecycle of an RNA such as folding, localization, processing, stability, ribosome assembly, and translational processes and are thus cru- cial regulators of the RNA metabolism. In plants, the nuclear/cytoplasmic epitranscriptome plays important roles in a wide range of biological processes, such as organ development, viral infection, and physiological means. Notably, recent transcriptome-wide analyses have also revealed novel dynamic modifications not only in plant nuclear/cytoplasmic RNAs related to photosynthesis but Citation: Manavski, N.; Vicente, A.; especially in chloroplast mRNAs, suggesting important and hitherto undefined regulatory steps in Chi, W.; Meurer, J.
    [Show full text]
  • 1.2 Cis Elements …………………………………………………………………
    UC Irvine UC Irvine Electronic Theses and Dissertations Title Characterization of the Mammalian mRNA 3' Processing Complex Permalink https://escholarship.org/uc/item/0m16c8r4 Author Chan, Serena Leong Publication Date 2014 Peer reviewed|Thesis/dissertation eScholarship.org Powered by the California Digital Library University of California UNIVERSITY OF CALIFORNIA, IRVINE Characterization of the Mammalian mRNA 3’ Processing Complex DISSERTATION submitted in partial satisfaction of the requirements for the degree of DOCTOR OF PHILOSOPHY in Biomedical Sciences by Serena Leong Chan Dissertation Committee: Professor Yongsheng Shi, Ph.D., Chair Professor Andrej Lupták, Ph.D. Professor Klemens J. Hertel, Ph.D. Professor Marian L. Waterman, Ph.D. 2014 1 Chapter 1 © 2010 John Wiley & Sons, Ltd. All Other Materials © 2014 Serena Leong Chan ii DEDICATION To my wonderful, loving mom for teaching me how to be a good person, for showing me the joys of life and for loving me for who I am. iii TABLE OF CONTENTS Page LIST OF FIGURES ……………………………….………………………………… v LIST OF TABLES ……………………………………..…………………………….. vii ACKNOWLEDGEMENTS ……………………………………………………….… viii CURRICULUM VITAE …………………………………………….………………... x ABSTRACT OF THE DISSERTATION …………………………………........... xiii Chapter 1. Introduction ………………………………………………………………… 1 1.1 Pre-mRNA 3’ Processing Components Overview ………………………… 4 1.2 Cis Elements ………………………………………………………………….. 4 1.3 Trans Factors ........................................................................................... 7 1.4 mRNA 3’ Processing Complex
    [Show full text]
  • Emerging Roles for Natural Microrna Sponges
    Emerging Roles for Natural MicroRNA Sponges The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Ebert, Margaret S., and Phillip A. Sharp. “Emerging Roles for Natural MicroRNA Sponges.” Current Biology 20, no. 19 (October 2010): R858–R861. © 2010 Elsevier. As Published http://dx.doi.org/10.1016/j.cub.2010.08.052 Publisher Elsevier B.V. Version Final published version Citable link http://hdl.handle.net/1721.1/96080 Terms of Use Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. Current Biology 20, R858–R861, October 12, 2010 ª2010 Elsevier Ltd All rights reserved DOI 10.1016/j.cub.2010.08.052 Emerging Roles for Natural MicroRNA Minireview Sponges Margaret S. Ebert and Phillip A. Sharp miRNAs in a variety of systems: in vitro differentiation of neurons [3] and mesenchymal stem cells [4]; xenografts of cancer cell lines [5,6]; and bone marrow reconstitutions Recently, a non-coding RNA expressed from a human from hematopoietic stem/progenitor cells [7–9]. Germline pseudogene was reported to regulate the corresponding transgenic fruitflies have been shown to generate hypomor- protein-coding mRNA by acting as a decoy for microRNAs phic miRNA phenotypes when sponge expression is induced (miRNAs) that bind to common sites in the 30 untranslated in a tissue-specific manner via the Gal4–UAS system [10]. regions (UTRs). It was proposed that competing for miRNAs might be a general activity of pseudogenes.
    [Show full text]
  • A Tale of Two Rnas During Viral Infection: How Viruses Antagonize Mrnas and Small Non-Coding Rnas in the Host Cell
    viruses Review A Tale of Two RNAs during Viral Infection: How Viruses Antagonize mRNAs and Small Non-Coding RNAs in The Host Cell Kristina M. Herbert 1,* and Anita Nag 2,* 1 Department of Experimental Microbiology, Center for Scientific Research and Higher Education of Ensenada (CICESE), Ensenada, Baja California 22860, Mexico 2 Department of Chemistry, Florida A&M University, Tallahassee, FL 32307, USA * Correspondence: [email protected] (K.M.H.); [email protected] (A.N.); Tel.: +52-646-175-0500 (K.M.H.); +1-850-399-5658 (A.N.) Academic Editor: Alexander Ploss Received: 29 March 2016; Accepted: 20 May 2016; Published: 2 June 2016 Abstract: Viral infection initiates an array of changes in host gene expression. Many viruses dampen host protein expression and attempt to evade the host anti-viral defense machinery. Host gene expression is suppressed at several stages of host messenger RNA (mRNA) formation including selective degradation of translationally competent messenger RNAs. Besides mRNAs, host cells also express a variety of noncoding RNAs, including small RNAs, that may also be subject to inhibition upon viral infection. In this review we focused on different ways viruses antagonize coding and noncoding RNAs in the host cell to its advantage. Keywords: mRNA; endonuclease; host shut-off; virus; RNAi 1. Introduction Viral infection has significant effects on the host’s gene expression program. Upon viral infection, mammalian cells activate specific gene expression pathways as a defense response. To assure survival, viruses manipulate the host’s gene expression response pattern in order to maximize viral replication and/or to evade detection by, and block the, host immune responses.
    [Show full text]
  • Murine Cytomegalovirus Encodes a Mir-27 Inhibitor Disguised As a Target
    Murine cytomegalovirus encodes a miR-27 inhibitor disguised as a target Valentina Libria,1, Aleksandra Helwakb,1, Pascal Miesenc, Diwakar Santhakumara,d, Jessica G. Borger a, Grzegorz Kudlab, Finn Greye, David Tollerveyb, and Amy H. Bucka,d,2 aCentre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom; bWellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom; cDepartment of Medical Microbiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands; dDivision of Pathway Medicine, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom; and eThe Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, United Kingdom Edited* by Norman R. Pace, University of Colorado, Boulder, CO, and approved November 29, 2011 (received for review September 1, 2011) Individual microRNAs (miRNAs) are rapidly down-regulated during involved (16). A small nuclear RNA (snRNA) in Herpesvirus conditions of cellular activation and infection, but factors mediat- saimiri (HVS), HSUR-1, was recently shown to bind to miR-27 ing miRNA turnover are poorly understood. Infection of mouse and mediate its degradation (17). However, no homolog of cells with murine cytomegalovirus (MCMV) induces the rapid HSUR-1 has been identified in other viral families. miRNA down-regulation of an antiviral cellular miRNA, miR-27. Here, we turnover mechanisms in animals remain poorly characterized identify a transcript produced by MCMV that binds to miR-27 and (18). The aim of this work was to identify miR-27 interaction sites mediates its degradation.
    [Show full text]
  • Viral Noncoding Rnas: More Surprises
    Downloaded from genesdev.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW Viral noncoding RNAs: more surprises Kazimierz T. Tycowski, Yang Eric Guo, Nara Lee, Walter N. Moss, Tenaya K. Vallery, Mingyi Xie, and Joan A. Steitz Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06536, USA Eukaryotic cells produce several classes of long and small • As for all investigations of viral infection, studying viral noncoding RNA (ncRNA). Many DNA and RNA viruses ncRNAs has richly enhanced our understanding of their synthesize their own ncRNAs. Like their host counter- host cells. In particular, surprising insights into the evo- parts, viral ncRNAs associate with proteins that are essen- lutionary relationships between viruses and their hosts tial for their stability, function, or both. Diverse biological have emerged. With increasing frequency, studies of vi- roles—including the regulation of viral replication, viral ral ncRNAs have led to novel insights into host cell persistence, host immune evasion, and cellular transfor- functioning. — mation have been ascribed to viral ncRNAs. In this re- • In some cases, synthesizing a ncRNA rather than a view, we focus on the multitude of functions played by protein may be the preferred mode of accomplishing a ncRNAs produced by animal viruses. We also discuss function for a virus. RNAs are less immunogenic and their biogenesis and mechanisms of action. therefore can more easily slip under the radar of the host cell immune system. • All viral ncRNAs—like host ncRNAs—associate with — — Like their host cells, many but not all viruses make proteins that are integral to their function.
    [Show full text]
  • The Exoribonuclease XRN2 and the RNA- Binding Proteins SART-3 and USIP-1
    Molecular and Developmental Analysis of Non-Coding RNA Metabolism in C. elegans: the Exoribonuclease XRN2 and the RNA- Binding Proteins SART-3 and USIP-1 Inauguraldissertation zur Erlangung der Würde eines Doktors der Philosophie vorgelegt der Philosophisch-Naturwissenschaftlichen Fakultät der Universität Basel von Stefan Rüegger Aus Maur, Schweiz Basel, 2014 Originaldokument gespeichert auf dem Dokumentenserver der Universität Basel edoc.unibas.ch Dieses Werk ist unter dem Vertrag „Creative Commons Namensnennung-Keine kommerzielle Nutzung- Keine Bearbeitung 3.0 Schweiz“ (CC BY-NC-ND 3.0 CH) lizenziert. Die vollständige Lizenz kann unter creativecommons.org/licenses/by-nc-nd/3.0/ch/ eingesehen werden. Genehmigt von der Philosophisch-Naturwissenschaftlichen Fakultät auf Antrag von Prof. Dr. Nancy Hynes, Dr. Helge Grosshans, Dr. Javier Martinez Basel, den 18.02.2014 Prof. Dr. Jörg Schibler (Dekan) Namensnennung-Keine kommerzielle Nutzung-Keine Bearbeitung 3.0 Schweiz (CC BY-NC-ND 3.0 CH) Sie dürfen: Teilen — den Inhalt kopieren, verbreiten und zugänglich machen Unter den folgenden Bedingungen: Namensnennung — Sie müssen den Namen des Autors/Rechteinhabers in der von ihm festgelegten Weise nennen. Keine kommerzielle Nutzung — Sie dürfen diesen Inhalt nicht für kommerzielle Zwecke nutzen. Keine Bearbeitung erlaubt — Sie dürfen diesen Inhalt nicht bearbeiten, abwandeln oder in anderer Weise verändern. Wobei gilt: Verzichtserklärung — Jede der vorgenannten Bedingungen kann aufgehoben werden, sofern Sie die ausdrückliche Einwilligung des Rechteinhabers
    [Show full text]
  • Regulation of RNA Stability by Terminal Nucleotidyltransferases
    Western University Scholarship@Western Electronic Thesis and Dissertation Repository 7-11-2019 10:30 AM Regulation of RNA stability by terminal nucleotidyltransferases Christina Z. Chung The University of Western Ontario Supervisor Heinemann, Ilka U. The University of Western Ontario Graduate Program in Biochemistry A thesis submitted in partial fulfillment of the equirr ements for the degree in Doctor of Philosophy © Christina Z. Chung 2019 Follow this and additional works at: https://ir.lib.uwo.ca/etd Part of the Biochemistry Commons Recommended Citation Chung, Christina Z., "Regulation of RNA stability by terminal nucleotidyltransferases" (2019). Electronic Thesis and Dissertation Repository. 6255. https://ir.lib.uwo.ca/etd/6255 This Dissertation/Thesis is brought to you for free and open access by Scholarship@Western. It has been accepted for inclusion in Electronic Thesis and Dissertation Repository by an authorized administrator of Scholarship@Western. For more information, please contact [email protected]. Abstract The dysregulation of RNAs has global effects on all cellular pathways. The regulation of RNA metabolism is thus tightly controlled. Terminal RNA nucleotidyltransferases (TENTs) regulate RNA stability and activity through the addition of non-templated nucleotides to the 3′-end. TENT-catalyzed adenylation and uridylation have opposing effects; adenylation stabilizes while uridylation silences or degrades RNA. All TENT homologs were initially characterized as adenylyltransferases; the identification of caffeine-induced death suppressor protein 1 (Cid1) in Schizosaccharomyces pombe as an uridylyltransferase led to the reclassification of many TENTs as uridylyltransferases. Cid1 uridylates mRNAs that are subsequently degraded by the exonuclease Dis-like 3′-5′ exonuclease 2 (Dis3L2), while the human homolog germline-development 2 (Gld2) has been associated with adenylation of mRNAs and miRNAs and uridylation of Group II pre-miRNAs.
    [Show full text]
  • Thesis Reference
    Thesis Structural and functional studies of poly(U) polymerases MUNOZ TELLO, Paola Andréa Abstract Nous avons étudié les aspects structuraux et fonctionnels de deux poly(U) polymérases (PUPs) afin de mieux comprendre le fonctionnement de ces enzymes: l'enzyme Cid1 PUP de Schizosaccharomyces pombe et l'enzyme RET1 de Trypanosome brucei. Ces protéines sont impliquées dans la polyuridylation de plusieurs types d'ARNs comme les ARNms ou les ARNgs. Nous avons déterminé la structure atomique par cristallographie aux rayons X de l'enzyme Cid1 liée à son substrat UTP, un UTP non hydrolysable et un pseudo-produit ApU qui correspondrait à la première étape de l'uridylation d'un ARNm polyadenylé. Récemment, nous avons obtenu des cristaux contenant un fragment fonctionnel de la protéine RET1 et la résolution de la structure est la prochaine étape. Nos études fournissent une vision atomique de la sélectivité envers l'UTP ainsi que la reconnaissance de l'ARN par les enzymes impliquées dans la polyuridylation en détaillant les mécanismes moléculaires de cette famille d'enzymes et de leurs complexes. Reference MUNOZ TELLO, Paola Andréa. Structural and functional studies of poly(U) polymerases . Thèse de doctorat : Univ. Genève, 2014, no. Sc. 4716 URN : urn:nbn:ch:unige-408396 DOI : 10.13097/archive-ouverte/unige:40839 Available at: http://archive-ouverte.unige.ch/unige:40839 Disclaimer: layout of this document may differ from the published version. 1 / 1 UNIVERSITÉ DE GENÈVE FACULTE DES SCIENCES Département de Biologie Moléculaire Professeur Stéphane Thore Structural and Functional Studies of Poly(U) Polymerases THÈSE Présentée à la faculté des sciences de l’Université de Genève pour obtenir le grade de Docteur ès Sciences, mention Biologie par Paola MUNOZ TELLO de Cali (COLOMBIE) THÈSE N° 4716 GENÈVE Atelier d’impression Repromail 2014 2 Acknowledgements First of all, I would like to thank the members of the jury, Professor Cecilia Arraiano, Professor Andrzej Dziembowski and Professor Thomas Schalch, for accepting to evaluate my thesis research.
    [Show full text]
  • Herpesvirus Saimiri Noncoding RNA Demián Cazalla, Et Al
    Down-Regulation of a Host MicroRNA by a Herpesvirus saimiri Noncoding RNA Demián Cazalla, et al. Science 328, 1563 (2010); DOI: 10.1126/science.1187197 This copy is for your personal, non-commercial use only. If you wish to distribute this article to others, you can order high-quality copies for your colleagues, clients, or customers by clicking here. Permission to republish or repurpose articles or portions of articles can be obtained by following the guidelines here. The following resources related to this article are available online at www.sciencemag.org (this infomation is current as of December 1, 2010 ): A correction has been published for this article at: http://www.sciencemag.org/content/329/5998/1467.3.full.html Updated information and services, including high-resolution figures, can be found in the online version of this article at: http://www.sciencemag.org/content/328/5985/1563.full.html Supporting Online Material can be found at: on December 1, 2010 http://www.sciencemag.org/content/suppl/2010/06/15/328.5985.1563.DC1.html A list of selected additional articles on the Science Web sites related to this article can be found at: http://www.sciencemag.org/content/328/5985/1563.full.html#related This article cites 24 articles, 16 of which can be accessed free: http://www.sciencemag.org/content/328/5985/1563.full.html#ref-list-1 This article has been cited by 1 articles hosted by HighWire Press; see: www.sciencemag.org http://www.sciencemag.org/content/328/5985/1563.full.html#related-urls This article appears in the following subject collections: Molecular Biology http://www.sciencemag.org/cgi/collection/molec_biol Downloaded from Science (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005.
    [Show full text]