DOCSLIB.ORG

Post-Transcriptional Regulation of Gene Expression in Response to Iron Deficiency in Saccharomyces Cerevisiae by Sandra Viviana

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Post-Transcriptional Regulation of Gene Expression in Response to Iron Deficiency in Saccharomyces Cerevisiae by Sandra Viviana Post-transcriptional Regulation of Gene Expression in Response to Iron Deficiency in Saccharomyces cerevisiae by Sandra Viviana Vergara Program in Genetics and Genomics Duke University Date:_______________________ Approved: ___________________________ Dennis J. Thiele, Ph.D., Supervisor ___________________________ Matthias Gromeier, M.D. ___________________________ Jack Keene, Ph.D. ___________________________ Daniel Lew, Ph.D. ___________________________ William Marzluff, Ph.D. Dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Program in Genetics and Genomics of Duke University 2010 ABSTRACT Post-transcriptional Regulation of Gene Expression in Response to Iron Deficiency in Saccharomyces cerevisiae by Sandra Viviana Vergara Program in Genetics and Genomics Duke University Date:_______________________ Approved: ___________________________ Dennis J. Thiele, Ph.D., Supervisor ___________________________ Matthias Gromeier, M.D. ___________________________ Jack Keene, Ph.D. ___________________________ Daniel Lew, Ph.D. ___________________________ William Marzluff, Ph.D. An abstract of a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Program in Genetics and Genomics in the Graduate School of Duke University 2010 Copyright by Sandra Viviana Vergara 2010 Abstract The ability of iron (Fe) to easily transition between two valence states makes it a preferred co-factor for innumerable biochemical reactions, ranging from cellular energy production, to oxygen transport, to DNA synthesis and chromatin modification. While Fe is highly abundant on the crust of the earth, its insolubility at neutral pH limits its bioavailability. As a consequence, organisms have evolved sophisticated mechanisms of adaptation to conditions of scarce Fe availability. Studies in the baker’s yeast Saccharomyces cerevisiae have shed light into the cellular mechanisms by which cells respond to limited Fe-availability. In response to Fe- deficiency, the transcription factors Aft1 and Aft2 activate a group of genes collectively known as the Fe-regulon. Genes in this group encode proteins involved in high-affinity plasma membrane Fe-transport and siderophore uptake, as well as Fe-mobilization from intracellular stores and heme re-utilization. Concomitant with the up-regulation of the Fe-regulon, a large number of mRNAs encoding Fe-dependent proteins as well as proteins involved in many Fe-dependent processes are markedly down regulated. Thus, in response to low Fe-levels the cell activates the Fe-uptake and mobilization systems, while down-regulating mRNAs involved in highly Fe-demanding processes leading to a genome-wide remodeling of cellular metabolism that permits the funneling of the limiting Fe to essential Fe-dependent reactions. iv The Fe-regulon member Cth2 belongs to a family of mRNA-binding proteins characterized by an RNA-binding motif consisting of two tandem zinc-fingers of the CX 8CX 5CX 3H type. Members of this family recognize and bind specific AU-rich elements (AREs) located in the 3’untranslated region (3’UTRs) of select groups of mRNAs, thereby promoting their rapid degradation. In response to Fe-limitation, Cth2 binds ARE sequences within the 3’UTRs of many mRNAs encoding proteins involved in Fe- homeostasis and Fe-dependent processes, thereby accelerating their rate of decay. Work described in this dissertation demonstrates that the Cth2 homolog , Cth1, is a bona fide member of the Fe-regulon, binds ARE-sequences within the 3’UTRs of select mRNAs and promotes their decay. Cth1 and Cth2 appear to be only partially redundant; Cth1 preferentially targets mRNAs encoding mitochondrial proteins, while Cth2 promotes the degradation of most of Cth1 targets in addition to other mitochondrial and non-mitochondrial Fe-requiring processes. The coordinated activity of Cth1 and Cth2 results in dramatic changes in glucose metabolism. In addition, experiments described in this dissertation indicate that the CTH1 and CTH2 transcripts are themselves subject to ARE-mediated regulation by the Cth1 and Cth2 proteins, creating an auto- and trans- regulatory circuit responsible for differences in their expression. Finally, work described here demonstrates that Cth2 is a nucleocytoplasmic shuttling protein and that shuttling is important for the early determination of cytosolic mRNA-fate. v Contents Abstract ......................................................................................................................................... iv List of Tables .................................................................................................................................. x List of Figures ............................................................................................................................... xi Acknowledgements .................................................................................................................. xiii 1. Introduction ............................................................................................................................... 1 1.1. Co-evolution of life and transition metal bioavailability ........................................... 1 1.2. Iron in biology – essential, harmful, and hard to get ................................................. 3 1.2.1. Iron-Sulfur clusters proteins ..................................................................................... 4 1.2.1. Heme proteins ............................................................................................................. 5 1.2.3. Other Fe-coordinating proteins ................................................................................ 6 1.3. Iron Homeostasis in bacteria ....................................................................................... 10 1.3.1. Iron uptake and storage ........................................................................................... 10 1.3.2 The ferric uptake repressor, Fur .............................................................................. 12 1.3.3 RyhB-mediated response to iron deficiency .......................................................... 13 1.4. Iron homeostasis in baker’s yeast ................................................................................ 14 1.4.1. Iron uptake and storage ........................................................................................... 14 1.4.2. Transcriptional regulation of iron homeostasis ................................................... 17 1.4.3. Post-transcriptional regulation of iron homeostasis ........................................... 20 1.4.4. Metabolic regulation of iron homeostasis ............................................................. 24 1.5. Iron homeostasis in mammals ..................................................................................... 26 1.5.1. Iron uptake and storage ........................................................................................... 26 vi 1.5.2. Systemic regulation of iron balance – hepcidin ................................................... 30 1.5.3. Cellular regulation of iron balance – the IRE/IRP system .................................. 31 1.5.4. Disorders of iron of balance .................................................................................... 32 1.6. Post-transcriptional regulation of mRNA stability by ARE-binding proteins ..... 35 1.6.1. Molecular mechanisms of mRNA decay ............................................................... 35 1.6.2. AU-rich elements (AREs) ........................................................................................ 39 1.6.3. ARE-binding proteins (AUBPs) .............................................................................. 40 1.6.3.1. CX 8CX 5CX 3H-proteins in mammals .................................................................... 42 1.6.4. ARE-mediated mRNA decay – AMD .................................................................... 46 1.7. CX 8CX 5CX 3H proteins in yeast – Cth1 and Cth2 ....................................................... 48 2. Cooperation of two mRNA-binding proteins drives metabolic adaptation to iron deficiency ..................................................................................................................................... 52 2.1 Introduction ..................................................................................................................... 52 2.2 Materials and Methods .................................................................................................. 55 2.3 Results .............................................................................................................................. 60 2.3.1 Cth1 function in response to Fe-deficiency ............................................................ 60 2.3.2 Aft1 and Aft2 regulate CTH1 transcription ........................................................... 63 2.3.3 Cth1 stimulates mRNA turnover ............................................................................ 66 2.3.4 Cth1 targets mRNAs mostly encoding mitochondrial proteins ......................... 70 2.3.5 Cth1/Cth2-dependent changes in carbohydrate metabolism .............................. 86 2.3.6 Iron deficiency elicits changes in glucose metabolism ......................................... 92 2.4 Discussion .......................................................................................................................
Load more

Recommended publications
  • Effect of a Caloric Restriction Based On
    UNIVERSIDAD AUTÓNOMA DE MADRID FACULTAD DE CIENCIAS DEPARTAMENTO DE BIOLOGÍA DOCTORAL THESIS Biology PhD “Effect of a caloric restriction based on the Mediterranean diet and intake of traditional Mediterranean foods on the expression of microRNAs regulating molecular processes associated with aging” INSTITUTO MADRILEÑO DE ESTUDIOS AVANZADOS EN ALIMENTACIÓN (IMDEA FOOD INSTITUTE) VÍCTOR MICÓ MORENO Madrid, 2018 UNIVERSIDAD AUTÓNOMA DE MADRID FACULTAD DE CIENCIAS DEPARTAMENTO DE BIOLOGÍA DOCTORAL THESIS Biology PhD “Effect of a caloric restriction based on the Mediterranean diet and intake of traditional Mediterranean foods on the expression of microRNAs regulating molecular processes associated with aging” INSTITUTO MADRILEÑO DE ESTUDIOS AVANZADOS EN ALIMENTACIÓN (IMDEA FOOD INSTITUTE) Memoria presentada por: Víctor Micó Moreno Para optar al grado de: DOCTOR EN BIOLOGÍA Doña Lidia Ángeles Daimiel Ruíz, Doctora en Biología Celular y Genética por la Universidad Autónoma de Madrid, investigadora del Instituto IMDEA Alimentación, informa favorablemente la solicitud de autorización de defensa de la tesis doctoral con el Título: “Effect of a caloric restriction based on the Mediterranean diet and intake of traditional Mediterranean foods on the expression of microRNAs regulating molecular processes associated with aging”, presentada por Don Víctor Micó Moreno para optar al grado de Doctor en Biología. Este trabajo ha sido realizado en el Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA Alimentación) bajo su dirección, y cumple satisfactoriamente las condiciones requeridas por el Departamento de Biología de la Universidad Autónoma de Madrid para optar al Título de Doctor. Ha actuado como tutor académico, y presenta su conformidad el Dr. Carlos Francisco Sentís Castaño, vicedecano de Personal Docente e Investigador y profesor titular del Departamento de Biología de la Facultad de Ciencias de la Universidad Autónoma de Madrid.
    [Show full text]
  • Yeast Genome Gazetteer P35-65
    gazetteer Metabolism 35 tRNA modification mitochondrial transport amino-acid metabolism other tRNA-transcription activities vesicular transport (Golgi network, etc.) nitrogen and sulphur metabolism mRNA synthesis peroxisomal transport nucleotide metabolism mRNA processing (splicing) vacuolar transport phosphate metabolism mRNA processing (5’-end, 3’-end processing extracellular transport carbohydrate metabolism and mRNA degradation) cellular import lipid, fatty-acid and sterol metabolism other mRNA-transcription activities other intracellular-transport activities biosynthesis of vitamins, cofactors and RNA transport prosthetic groups other transcription activities Cellular organization and biogenesis 54 ionic homeostasis organization and biogenesis of cell wall and Protein synthesis 48 plasma membrane Energy 40 ribosomal proteins organization and biogenesis of glycolysis translation (initiation,elongation and cytoskeleton gluconeogenesis termination) organization and biogenesis of endoplasmic pentose-phosphate pathway translational control reticulum and Golgi tricarboxylic-acid pathway tRNA synthetases organization and biogenesis of chromosome respiration other protein-synthesis activities structure fermentation mitochondrial organization and biogenesis metabolism of energy reserves (glycogen Protein destination 49 peroxisomal organization and biogenesis and trehalose) protein folding and stabilization endosomal organization and biogenesis other energy-generation activities protein targeting, sorting and translocation vacuolar and lysosomal
    [Show full text]
  • Enzymes and Rna Complexes
    ENZYMES AND RNA COMPLEXES Mediator NMD Exosome NMD TRAMP/NNS Integrator Microprocessor RNA PROCESSING and DECAY machinery: RNases Protein Function Characteristics Exonucleases 5’ 3’ Xrn1 cytoplasmic, mRNA degradation processsive Rat1 nuclear, pre-rRNA, sn/snoRNA, pre-mRNA processing and degradation Rrp17/hNol12 nuclear, pre-rRNA processing Exosome 3’ 5’ multisubunit exo/endo complex subunits organized as in bacterial PNPase Rrp44/Dis3 catalytic subunit Exo/PIN domains, processsive Rrp4, Rrp40 pre-rRNA, sn/snoRNA processing, mRNA degradation Rrp41-43, 45-46 participates in NMD, ARE-dependent, non-stop decay Mtr3, Ski4 Mtr4 nuclear helicase cofactor DEAD box Rrp6 (Rrp47) nuclear exonuclease ( Rrp6 BP, cofactor) RNAse D homolog, processsive Ski2,3,7,8 cytoplasmic exosome cofactors. SKI complex helicase, GTPase Other 3’ 5’ Rex1-4 3’-5’ exonucleases, rRNA, snoRNA, tRNA processing RNase D homolog DXO 3’-5’ exonuclease in addition to decapping mtEXO 3’ 5’ mitochondrial degradosome RNA degradation in yeast Suv3/ Dss1 helicase/ 3’-5’ exonuclease DExH box/ RNase II homolog Deadenylation Ccr4/NOT/Pop2 major deadenylase complex (Ccr, Caf, Pop, Not proteins) Ccr4- Mg2+ dependent endonuclease Pan2p/Pan3 additional deadenylases (poliA tail length) RNase D homolog, poly(A) specific nuclease PARN mammalian deadenylase RNase D homolog, poly(A) specific nuclease Endonucleases RNase III -Rnt1 pre-rRNA, sn/snoRNA processing, mRNA degradation dsRNA specific -Dicer, Drosha siRNA/miRNA biogenesis, functions in RNAi PAZ, RNA BD, RNase III domains Ago2 Slicer
    [Show full text]
  • A Disease-Linked Lncrna Mutation in Rnase MRP Inhibits Ribosome Synthesis
    bioRxiv preprint doi: https://doi.org/10.1101/2021.03.29.437572; this version posted March 29, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. A disease-linked lncRNA mutation in RNase MRP inhibits ribosome synthesis Nic Roberston1, Vadim Shchepachev1, David Wright2, Tomasz W. Turowski1, Christos Spanos1, Aleksandra Helwak1, Rose Zamoyska2, David Tollervey1 1 Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, UK 2 Ashworth Laboratories, Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, UK Keywords: protein-RNA interaction; RNA-binding sites; UV crosslinking; mass spectrometry; genetic disease; Cartilage Hair Hypoplasia; ribosome synthesis; T cell activation Running title: RNase MRP defects cause ribosomopathy Highlights: • Mutations in RMRP lncRNA impair pre-rRNA processing and T cell activation • Patient derived fibroblasts show impaired pre-rRNA processing • Cells with the most common disease-linked mutation have specific processing defects • Cytoplasmic ribosomes and intact RNase MRP complexes are also reduced in these cells 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.03.29.437572; this version posted March 29, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Abstract Mutations in the human RMRP gene cause Cartilage Hair Hypoplasia (CHH), an autosomal recessive disorder characterized by skeletal abnormalities and impaired T cell activation.
    [Show full text]
  • A Specialized Processing Body That Is Temporally and Asymmetrically Regulated During the Cell Cycle in Saccharomyces Cerevisiae
    JCB: ARTICLE A specialized processing body that is temporally and asymmetrically regulated during the cell cycle in Saccharomyces cerevisiae Tina Gill, Jason Aulds, and Mark E. Schmitt Department of Biochemistry and Molecular Biology, State University of New York Upstate Medical University, Syracuse, NY 13210 Nase mitochondrial RNA processing (MRP) is an this spot was asymmetrically found in daughter cells, essential ribonucleoprotein endoribonuclease that where the RNase MRP substrate, CLB2 mRNA, localizes. R functions in the degradation of specifi c mRNAs in- Both the mitotic exit network and fourteen early ana- volved in cell cycle regulation. We have investigated phase release pathways are nonessential but important where this processing event occurs and how it is regu- for the temporal changes in localization. Asymmetric lo- lated. As expected, results demonstrate that RNase MRP calization was found to be dependent on the locasome. is predominantly localized in the nucleolus, where it The evidence suggests that these spots are specialized processes ribosomal RNAs. However, after the initiation processing bodies for the degradation of transcripts that of mitosis, RNase MRP localizes throughout the entire are cell cycle regulated and daughter cell localized. We nucleus and in a single discrete cytoplasmic spot that have called these TAM bodies for temporal asymmetric persists until the completion of telophase. Furthermore, MRP bodies. Introduction RNase mitochondrial RNA processing (MRP) is an essential ri- 27SA preribosomal RNA at the A3 site, forming the 5.8S(s) bonucleoprotein endoribonuclease that cleaves RNA substrates ribosomal RNA (rRNA; Schmitt and Clayton, 1993; Lygerou in a site-specifi c manner and is highly conserved in eukaryotes et al., 1996).
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2010/0267582 A1 BARD Et Al
    US 2010O267582A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0267582 A1 BARD et al. (43) Pub. Date: Oct. 21, 2010 (54) DIFFERENTAL, EXPRESSION OF (60) Provisional application No. 60/575.279, filed on May MOLECULES ASSOCATED WITH ACUTE 27, 2004. STROKE Publication Classification (75) Inventors: ALISON E. BARD, BETHESDA, MD (US); DAVID F. MOORE, (51) Int. Cl. ROCKVILLE, MD (US); EHUD C40B 30/04 (2006.01) GOLDIN, ROCKVILLE, MD (US) CI2O I/68 (2006.01) C40B 40/08 (2006.01) Correspondence Address: KLARQUIST SPARKMAN, LLP (OTT-NIH) (52) U.S. Cl. .................................... 506/9; 435/6; 506/17 121 S.W. SALMONSTREET, SUITE #1600 PORTLAND, OR 97204-2988 (US) (57) ABSTRACT (73) Assignees: THE GOVERNMENT OF THE Methods are provided for evaluating a stroke, for example for UNITED STATES OF AMERICA determining whether a subject has had an ischemic stroke, AS REPRESENTED BY THE determining the severity or likely neurological recovery of a SECRETARY OF THE Subject who has had an ischemic stroke, and determining a DEPARTMENT: OF HEALTH treatment regimen for a subject who has had an ischemic AND HUMAN SERVICES stroke, as are arrays and kits that can be used to practice the methods. In particular examples, the method includes screen (21) Appl. No.: 12/829,229 ing for expression in ischemic stroke related genes (or pro teins), such as white blood cell activation and differentiation (22) Filed: Jul. 1, 2010 genes (or proteins), genes (or proteins) related to hypoxia, genes (or proteins) involved in vascular repair, and genes (or Related U.S. Application Data proteins) related to a specific peripheral blood mononuclear (60) Division of application No.
    [Show full text]
  • Figure S1. HAEC ROS Production and ML090 NOX5-Inhibition
    Figure S1. HAEC ROS production and ML090 NOX5-inhibition. (a) Extracellular H2O2 production in HAEC treated with ML090 at different concentrations and 24 h after being infected with GFP and NOX5-β adenoviruses (MOI 100). **p< 0.01, and ****p< 0.0001 vs control NOX5-β-infected cells (ML090, 0 nM). Results expressed as mean ± SEM. Fold increase vs GFP-infected cells with 0 nM of ML090. n= 6. (b) NOX5-β overexpression and DHE oxidation in HAEC. Representative images from three experiments are shown. Intracellular superoxide anion production of HAEC 24 h after infection with GFP and NOX5-β adenoviruses at different MOIs treated or not with ML090 (10 nM). MOI: Multiplicity of infection. Figure S2. Ontology analysis of HAEC infected with NOX5-β. Ontology analysis shows that the response to unfolded protein is the most relevant. Figure S3. UPR mRNA expression in heart of infarcted transgenic mice. n= 12-13. Results expressed as mean ± SEM. Table S1: Altered gene expression due to NOX5-β expression at 12 h (bold, highlighted in yellow). N12hvsG12h N18hvsG18h N24hvsG24h GeneName GeneDescription TranscriptID logFC p-value logFC p-value logFC p-value family with sequence similarity NM_052966 1.45 1.20E-17 2.44 3.27E-19 2.96 6.24E-21 FAM129A 129. member A DnaJ (Hsp40) homolog. NM_001130182 2.19 9.83E-20 2.94 2.90E-19 3.01 1.68E-19 DNAJA4 subfamily A. member 4 phorbol-12-myristate-13-acetate- NM_021127 0.93 1.84E-12 2.41 1.32E-17 2.69 1.43E-18 PMAIP1 induced protein 1 E2F7 E2F transcription factor 7 NM_203394 0.71 8.35E-11 2.20 2.21E-17 2.48 1.84E-18 DnaJ (Hsp40) homolog.
    [Show full text]
  • The Rnase MRP and Rnase P Complexes, Will Be Summarised
    PDF hosted at the Radboud Repository of the Radboud University Nijmegen The following full text is a publisher's version. For additional information about this publication click this link. http://hdl.handle.net/2066/19147 Please be advised that this information was generated on 2021-09-28 and may be subject to change. The human The human RNase MRP complex RNase MRP complex Composition, assembly and role in human disease Hans van Eenennaam Hans van Eenennaam The human RNase MRP complex Composition, assembly and role in human disease Hans van Eenennaam, 2002 The human RNase MRP complex Composition, assembly and role in human disease een wetenschappelijke proeve op het gebied van de Natuurwetenschappen, Wiskunde en Informatica PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Katholieke Universiteit Nijmegen, volgens besluit van het College van Decanen in het openbaar te verdedigen op vrijdag 14 juni 2002 des namiddags om 1:30 uur precies door Hans van Eenennaam Cover illustration Statue of the Dwarf Seneb and his family, painted limestone, height 34 cm, width 22.5 cm, geboren op 3 november 1973 Giza, Tomb of Seneb, Late Fifth - Early Sixth te Middelburg Dynasty. From: The Cairo museum Masterpieces of Egyptian Art, Francesco Tiradritti, Thames & Hudson Ltd, London, 1998 Promotor Prof. Dr. W.J. van Venrooij Co-promotor Dr. G.J.M. Pruijn voor mijn ouders Manuscriptcommissie Prof. Dr. L.B.A. van de Putte Prof. Dr. F.P.J.T. Rutjes Prof. Dr. H.F. Tabak (Universiteit van Amsterdam) ISBN 90-9015696-8 © 2002 by Hans van Eenennaam The research described in this thesis was performed at the Department of Biochemistry, Faculty of Science, University of Nijmegen, the Netherlands.
    [Show full text]
  • A Novel Model for the Rnase MRP-Induced Switch Between the Different Forms of 5.8S Rrna
    Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 29 April 2021 doi:10.20944/preprints202104.0765.v1 Research article A novel model for the RNase MRP-induced switch between the different forms of 5.8S rRNA Xiao Li1,2,3, Janice M Zengel1 and Lasse Lindahl1 1 Department of Biological Sciences, University of Maryland Baltimore County (UMBC) 1000 Hilltop Circle, Baltimore, Maryland 21250, USA 2 Department of Biology, University of Rochester, Rochester, New York 14627, USA 3 Current address: Abbott Laboratories, San Diego, CA ribosome biogenesis; rRNA processing; RNase MRP; long/short 5.8S rRNA © 2021 by the author(s). Distributed under a Creative Commons CC BY license. Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 29 April 2021 doi:10.20944/preprints202104.0765.v1 Abstract: Processing of the RNA polymerase I pre-rRNA transcript into the mature 18S, 5.8S, and 25S rRNAs requires removing the “spacer” sequences. The canonical pathway for the removal of the ITS1 spacer, located between 18S and 5.8S rRNAs in the primary transcript, involves cleavages at the 3’ end of 18S rRNA and at two sites inside ITS1. The process generates a long and a short 5.8S rRNA that differ in the number of ITS1 nucleotides retained at the 5.8S 5’ end. Here we document a novel pathway that generates the long 5.8S for ITS1 while bypassing cleavage within ITS1. It entails a single endonuclease cut at the 3’-end of 18S rRNA followed by exonuclease Xrn1 degradation of ITS1. Mutations in RNase MRP increase the accumulation of long relative to short 5.8S rRNA; traditionally this is attributed to a decreased rate of RNase MRP cleavage at its target in ITS1, called A3.
    [Show full text]
  • Subject Index Proc
    13088 Subject Index Proc. Natl. Acad. Sci. USA 91 (1994) Apoptosis in substantia nigra following developmental striatal excitotoxic Brine shrimp injury, 8117 See Artemia Visualizing hippocampal synaptic function by optical detection of Ca2l Broccol entry through the N-methyl-D-aspartate channel, 8170 See Brassica Amygdala modulation of hippocampal-dependent and caudate Bromophenacyl bromide nucleus-dependent memory processes, 8477 Bromophenacyl bromide binding to the actin-bundling protein I-plastin Distribution of corticotropin-releasing factor receptor mRNA expression inhibits inositol trisphosphate-independent increase in Ca2l in human in the rat brain and pituitary, 8777 neutrophils, 3534 Brownian dynamics Preproenkephalin promoter yields region-specific and long-term Adhesion of hard spheres under the influence of double-layer, van der expression in adult brain after direct in vivo gene transfer via a Waals, and gravitational potentials at a solid/liquid interface, 3004 defective herpes simplex viral vector, 8979 Browsers Intravenous administration of a transferrin receptor antibody-nerve Thorn-like prickles and heterophylly in Cyanea: Adaptations to extinct growth factor conjugate prevents the degeneration of cholinergic avian browsers on Hawaii?, 2810 striatal neurons in a model of Huntington disease, 9077 Bruton agammaglobulinemia Axotomy induces the expression of vasopressin receptors in cranial and Genomic organization and structure of Bruton agammaglobulinemia spinal motor nuclei in the adult rat, 9636 tyrosine kinase: Localization
    [Show full text]
  • Human Ribonuclease P: Subunits, Function, and Intranuclear Localization
    Downloaded from rnajournal.cshlp.org on September 23, 2021 - Published by Cold Spring Harbor Laboratory Press RNA (2002), 8:1–7+ Cambridge University Press+ Printed in the USA+ Copyright © 2002 RNA Society+ DOI: 10+1017+S1355838201011189 REVIEW Human ribonuclease P: Subunits, function, and intranuclear localization NAYEF JARROUS Department of Molecular Biology, The Hebrew University–Hadassah Medical School, Jerusalem 91120, Israel ABSTRACT Catalytic complexes of nuclear ribonuclease P (RNase P) ribonucleoproteins are composed of several protein sub- units that appear to have specific roles in enzyme function in tRNA processing. This review describes recent progress made in the characterization of human RNase P, its relationship with the ribosomal RNA processing ribonucleoprotein RNase MRP, and the unexpected evolutionary conservation of its subunits. A new model for the biosynthesis of human RNase P is presented, in which this process is dynamic, transcription-dependent, and implicates functionally distinct nuclear compartments in tRNA biogenesis. Keywords: Cajal bodies; catalytic ribonucleoprotein; nucleolus; RNase MRP; RNase P; tRNA RIBONUCLEOPROTEIN COMPLEXES a ribonucleoprotein complex (Rossmanith et al+, 1995; OF RNase P Rossmanith & Karwan, 1998)+ These opposing find- ings provoke further debate on the biochemical nature Extensive purification analysis of RNase P from HeLa of mitochondrial and other organellar RNase P en- cells has revealed that the nuclear form of this tRNA zymes (Frank & Pace, 1998; Schon, 1999; Altman et al+,
    [Show full text]
  • Genome-Wide Investigation of Cellular Functions for Trna Nucleus
    Genome-wide Investigation of Cellular Functions for tRNA Nucleus- Cytoplasm Trafficking in the Yeast Saccharomyces cerevisiae DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Hui-Yi Chu Graduate Program in Molecular, Cellular and Developmental Biology The Ohio State University 2012 Dissertation Committee: Anita K. Hopper, Advisor Stephen Osmani Kurt Fredrick Jane Jackman Copyright by Hui-Yi Chu 2012 Abstract In eukaryotic cells tRNAs are transcribed in the nucleus and exported to the cytoplasm for their essential role in protein synthesis. This export event was thought to be unidirectional. Surprisingly, several lines of evidence showed that mature cytoplasmic tRNAs shuttle between nucleus and cytoplasm and their distribution is nutrient-dependent. This newly discovered tRNA retrograde process is conserved from yeast to vertebrates. Although how exactly the tRNA nuclear-cytoplasmic trafficking is regulated is still under investigation, previous studies identified several transporters involved in tRNA subcellular dynamics. At least three members of the β-importin family function in tRNA nuclear-cytoplasmic intracellular movement: (1) Los1 functions in both the tRNA primary export and re-export processes; (2) Mtr10, directly or indirectly, is responsible for the constitutive retrograde import of cytoplasmic tRNA to the nucleus; (3) Msn5 functions solely in the re-export process. In this thesis I focus on the physiological role(s) of the tRNA nuclear retrograde pathway. One possibility is that nuclear accumulation of cytoplasmic tRNA serves to modulate translation of particular transcripts. To test this hypothesis, I compared expression profiles from non-translating mRNAs and polyribosome-bound translating mRNAs collected from msn5Δ and mtr10Δ mutants and wild-type cells, in fed or acute amino acid starvation conditions.
    [Show full text]