DOCSLIB.ORG

Small Bristles, the Drosophila Ortholog of NXF-1, Is Essential for Mrna Export Throughout Development

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Small Bristles, the Drosophila Ortholog of NXF-1, Is Essential for Mrna Export Throughout Development Downloaded from rnajournal.cshlp.org on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press RNA (2001), 7:1781–1792+ Cambridge University Press+ Printed in the USA+ Copyright © 2001 RNA Society+ DOI: 10+1017+S1355838201014121 Small bristles, the Drosophila ortholog of NXF-1, is essential for mRNA export throughout development GAVIN S. WILKIE,1,4 VITALY ZIMYANIN,1,5 RUTH KIRBY,1 CHRISTOPHER KOREY,2 HELEN FRANCIS-LANG,3,6 DAVID VAN VACTOR,2 and ILAN DAVIS1 1 Wellcome Trust Centre for Cell Biology, Institute of Cell and Molecular Biology, King’s Buildings, University of Edinburgh, Edinburgh EH9 3JR, Scotland, United Kingdom 2 Harvard Medical School, Harvard University, Boston, Massachusetts 02115, USA 3 Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California 95064, USA ABSTRACT We identified a temperature-sensitive allele of small bristles (sbr ), the Drosophila ortholog of human TAP/NXF-1 and yeast Mex67, in a screen for mutants defective in mRNA export. We show that sbr is essential for the nuclear export of all mRNAs tested in a wide range of tissues and times in development. High resolution and sensitive in situ hybridization detect the rapid accumulation of individual mRNA species in sbr mutant nuclei in particles that are distinct from nascent transcript foci and resemble wild-type export intermediates. The particles become more nu- merous and intense with increasing time at the restrictive temperature and are exported very rapidly after shifting back to the permissive temperature. The mRNA export block is not due indirectly to a defect in splicing, nuclear protein import, or aberrant nuclear ultrastructure, suggesting that in sbr mutants, mRNA is competent for export but fails to dock or translocate through NPCs. We conclude that NXF-1 is an essential ubiquitous export factor for all mRNAs throughout development in higher eukaryotes. Keywords: Drosophila; intracellular mRNA localization; Mex67; mRNA nuclear export; NXF-1; small bristles (sbr); TAP INTRODUCTION a role in mRNA export from the nucleus (reviewed in Conti & Izaurralde, 2001)+ For example, microinjection mRNA export from the nucleus is essential for gene of anti-GLE1 antibodies into cultured cells causes nu- expression and most of the factors required for this clear accumulation of poly(A)1 RNA (Watkins et al+, process have been characterized in yeast+ Although 1998)+ Transcript export efficiency is reduced when mu- many orthologs of the yeast proteins have also been tant forms of the DBP5 protein are injected into Xeno- identified in higher eukaryotes, it has proven difficult to pus oocytes (Schmitt et al+, 1999)+ RAE1, the ortholog study their role in mRNA export due to the lack of an of yeast GLE2, shuttles between the nucleus and cyto- in vitro nuclear mRNA export assay and absence of plasm in Xenopus oocytes and binds the nucleoporin mutations in the genes+ Nevertheless, in mammalian NUP98 (Pritchard et al+, 1999)+ Overexpression of the cultured cells, considerable circumstantial evidence sug- domain of NUP98 that binds to RAE1 causes nuclear gests that GLE1, DBP5, RAE1, and TAP/NXF1 all have accumulation of poly(A)1 RNA, a phenotype that is abrogated by excess RAE1 (Pritchard et al+, 1999)+ It is Reprint requests to: Ilan Davis, Wellcome Trust Centre for Cell , , , therefore likely that all these factors contribute to mRNA Biology Institute of Cell and Molecular Biology King’s Buildings Uni- + versity of Edinburgh, Edinburgh EH9 3JR, Scotland, United King- export dom; e-mail: ilan+davis@ed+ac+uk+ The best characterized mRNA export factor in higher 4 Present address: MRC Human Genetics Unit, Western General eukaryotes is TAP/NXF1, the cellular cofactor required Hospital, Crewe Road, Edinburgh, EH4 2XU, Scotland, United Kingdom+ for the nuclear export of unspliced retroviral RNA con- 5 Present address: Wellcome Trust/CRC Centre for Developmen- taining a constitutive transport element (CTE; Gruter tal Biology, Tennis Court Road, University of Cambridge, Cambridge +, + , + et al 1998) TAP is a member of a family of five human CB2 1QR United Kingdom ; +, , 6 Present address: Exelixis, Inc+, 170 Harbor Avenue, P+O+ Box nuclear export factors (NXFs Herold et al 2000 re- 511 S+, San Francisco, California 94083, USA+ viewed in Conti & Izaurralde, 2001)+ In Saccharomyces 1781 Downloaded from rnajournal.cshlp.org on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press 1782 G.S. Wilkie et al. cerevisiae, the only NXF gene, MEX67, is required for NXF1, whereas NXF3 does not (Herold et al+, 2000)+ In mRNA export together with MTR2 (Santos-Rosa et al+, C. elegans, RNAi against NXF1 causes lethality in both 1998)+ Both genes are essential and their mutations adult and embryonic stages and leads to nuclear ac- lead to mRNA export defects (Segref et al+, 1997)+ In cumulation of poly(A)1 RNA (Tan et al+, 2000)+ How- contrast, mex67 1, the only NXF gene in Schizosac- ever, this defect occurs a relatively long time after RNAi charomyces pombe, is not essential for growth or mRNA treatment, and it is unclear whether the block in mRNA nuclear export, but mex67 mutations are synthetic lethal export is due to indirect affects, such as aberrant splic- with rae1 (Yoon et al+, 2000)+ S. pombe rae1 1 is required ing, or defective nuclear ultrastructure+ Furthermore, for mRNA export (Brown et al+, 1995), as is GLE2, the the effects on individual mRNAs have not been inves- S. cerevisiae ortholog (Murphy et al+, 1996)+ These re- tigated in nematodes+ Moreover, in yeast, the precise sults indicate that Mex67 protein has a contributory intranuclear location of specific yeast mRNAs is diffi- rather than key role in mRNA export in S. pombe and cult to determine under the light microscope because may be an accessory factor for Rae1-mediated export of the small size of the nucleus+ Although some studies (Yoon et al+, 2000)+ suggest that mRNAs accumulate all over the nucleo- There is considerable circumstantial evidence sug- plasm when mRNA export is blocked (Hurt et al+, 2000), gesting that TAP/NXF1 is required for cellular mRNA other experiments show accumulation only at the site exported in higher eukaryotes+ Excess CTE RNA in- of transcription (Jensen et al+, 2001)+ hibits mRNA export in Xenopus oocytes, a phenotype Here, we address the role of TAP/NXF1 in Drosoph- abrogated by excess TAP (Gruter et al+, 1998)+ TAP ila in the export of specific transcripts by studying heterodimerizes with p15, the analog of yeast Mtr2p, mutations in the gene using high resolution in situ hy- and also interacts with RAE1 and the nucleoporins bridization+ We identified a temperature-sensitive (ts) NUP98, NUP214, NUP88, and NUP93 (Katahira et al+, allele of NXF1 in a screen for mutations that disrupts 1999; Bachi et al+, 2000; Suyama et al+, 2000)+ Further- mRNA export and show that the gene is encoded by more, TAP can be crosslinked to Poly(A)1 RNA and small bristles (sbr ), a previously uncloned locus with shuttles between the nucleus and cytoplasm by trans- several existing mutations (Lindsley & Zimm, 1992)+ portin-mediated nuclear import and export as a com- We show that Sbr is required for the nuclear export of plex with mRNA (Bear et al+, 1999; Kang & Cullen, all mRNA tested in many different kinds of tissues 1999; Bachi et al+, 2000)+ TAP also interacts with REF throughout development+ Two different ts alleles of sbr proteins, which are recruited to pre-mRNA processing cause a rapid nuclear accumulation of mRNA from all complexes and target mature mRNA for export (Le Hir genes tested in distinct particles, which are distributed et al+, 2000; Stutz et al+, 2000; Zhou et al+, 2000; Rod- throughout the nucleoplasm+ The accumulated intra- rigues et al+, 2001)+ Human TAP and p15 together can nuclear particles do not contain introns, and the phe- functionally complement mex67mtr2 double knockout notype is rapidly reversible by shifting back to the in yeast, and are therefore likely to perform conserved permissive temperature, suggesting that the mRNA is functions in nuclear mRNA export (Katahira et al+, 1999)+ competent for export+ We also show that the pheno- Furthermore, overexpression of TAP/p15 heterodimers type of sbr alleles is not due to an aberrant nuclear stimulates export of RNAs that are otherwise ineffi- ultrastructure or defect in nuclear protein import+ To- ciently exported in cultured cells and in Xenopus oo- gether, our results suggest that sbr mutations prevent cytes (Braun et al+, 2001; Guzik et al+, 2001)+ the docking or translocation of mRNA export intermedi- However, TAP/NXF1 has not been shown directly to ates that are otherwise competent export cargo+ be required for mRNA export in vertebrates+ Further- more, TAP/NXF1 is a member of a family of two in Caenorhabditis elegans, four in Drosophila, and at least RESULTS five in humans (Herold et al+, 2000)+ There are also two p15 orthologs (p15-1/NXT1 p15-2/NXT2) in humans, Identification of a ts mutation in all of which bind multiple NXF proteins (Herold et al+, small bristles that disrupts mRNA 2000)+ It is therefore unclear what combinations of NXF export from blastoderm nuclei and p15 are universally required for mRNA export and whether different members of the family have special- To isolate mutations that disrupt mRNA export in Dro- ized roles in the export of subclasses of mRNAs or at sophila, we screened a collection of X-linked ts lethal different times or tissues in development+ Although mutations (MacDougall et al+, 2001) generated by Helen
Load more

Recommended publications
  • Non-Synonymous Mutations Mapped to Chromosome X Associated With
    de Camargo et al. BMC Genomics (2015) 16:384 DOI 10.1186/s12864-015-1595-0 RESEARCH ARTICLE Open Access Non-synonymous mutations mapped to chromosome X associated with andrological and growth traits in beef cattle Gregório Miguel Ferreira de Camargo1,2,3, Laercio R Porto-Neto2, Matthew J Kelly3, Rowan J Bunch2, Sean M McWilliam2, Humberto Tonhati1, Sigrid A Lehnert2, Marina R S Fortes3* and Stephen S Moore4 Abstract Background: Previous genome-wide association analyses identified QTL regions in the X chromosome for percentage of normal sperm and scrotal circumference in Brahman and Tropical Composite cattle. These traits are important to be studied because they are indicators of male fertility and are correlated with female sexual precocity and reproductive longevity. The aim was to investigate candidate genes in these regions and to identify putative causative mutations that influence these traits. In addition, we tested the identified mutations for female fertility and growth traits. Results: Using a combination of bioinformatics and molecular assay technology, twelve non-synonymous SNPs in eleven genes were genotyped in a cattle population. Three and nine SNPs explained more than 1% of the additive genetic variance for percentage of normal sperm and scrotal circumference, respectively. The SNPs that had a major influence in percentage of normal sperm were mapped to LOC100138021 and TAF7L genes; and in TEX11 and AR genes for scrotal circumference. One SNP in TEX11 was explained ~13% of the additive genetic variance for scrotal circumference at 12 months. The tested SNP were also associated with weight measurements, but not with female fertility traits.
    [Show full text]
  • Implication of PIWI Interacting Rnas Karine Casier, Antoine Boivin, Clément Carré, Laure Teysset
    Environmentally-Induced Transgenerational Epigenetic Inheritance: Implication of PIWI Interacting RNAs Karine Casier, Antoine Boivin, Clément Carré, Laure Teysset To cite this version: Karine Casier, Antoine Boivin, Clément Carré, Laure Teysset. Environmentally-Induced Transgen- erational Epigenetic Inheritance: Implication of PIWI Interacting RNAs. Cells, MDPI, 2019, 8 (9), pp.1108. 10.3390/cells8091108. hal-02344602 HAL Id: hal-02344602 https://hal.sorbonne-universite.fr/hal-02344602 Submitted on 4 Nov 2019 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. cells Review Environmentally-Induced Transgenerational Epigenetic Inheritance: Implication of PIWI Interacting RNAs Karine Casier , Antoine Boivin , Clément Carré and Laure Teysset * Transgenerational Epigenetics & small RNA Biology, Sorbonne Université, CNRS, Laboratoire Biologie du Développement, Institut de Biologie Paris-Seine, UMR7622, 75005 Paris, France; [email protected] (K.C.); [email protected] (A.B.); [email protected] (C.C.) * Correspondence: [email protected] Received: 16 August 2019; Accepted: 17 September 2019; Published: 19 September 2019 Abstract: Environmentally-induced transgenerational epigenetic inheritance is an emerging field. The understanding of associated epigenetic mechanisms is currently in progress with open questions still remaining. In this review, we present an overview of the knowledge of environmentally-induced transgenerational inheritance and associated epigenetic mechanisms, mainly in animals.
    [Show full text]
  • Genome-Wide Mapping in a House Mouse Hybrid Zone Reveals Hybrid Sterility Loci and Dobzhansky-Muller Interactions Leslie M Turner1,2, Bettina Harr1*
    RESEARCH ARTICLE elifesciences.org Genome-wide mapping in a house mouse hybrid zone reveals hybrid sterility loci and Dobzhansky-Muller interactions Leslie M Turner1,2, Bettina Harr1* 1Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Biology, Plön, Germany; 2Laboratory of Genetics, University of Wisconsin, Madison, United States Abstract Mapping hybrid defects in contact zones between incipient species can identify genomic regions contributing to reproductive isolation and reveal genetic mechanisms of speciation. The house mouse features a rare combination of sophisticated genetic tools and natural hybrid zones between subspecies. Male hybrids often show reduced fertility, a common reproductive barrier between incipient species. Laboratory crosses have identified sterility loci, but each encompasses hundreds of genes. We map genetic determinants of testis weight and testis gene expression using offspring of mice captured in a hybrid zone between M. musculus musculus and M. m. domesticus. Many generations of admixture enables high-resolution mapping of loci contributing to these sterility-related phenotypes. We identify complex interactions among sterility loci, suggesting multiple, non-independent genetic incompatibilities contribute to barriers to gene flow in the hybrid zone. DOI: 10.7554/eLife.02504.001 Introduction *For correspondence: harr@ New species arise when reproductive barriers form, preventing gene flow between populations evolbio.mpg.de (Coyne and Orr, 2004). Recently, two approaches have substantially
    [Show full text]
  • The Role of Lissencephaly-1 Protein in Male Germ Cell Differentiation
    THE ROLE OF LISSENCEPHALY-1 PROTEIN IN MALE GERM CELL DIFFERENTIATION Dissertation zur Erlangung des Doktorgrades der Mathematisch-Naturwissenschaftlichen Fakultäten der Georg-August-Universität zu Göttingen vorgelegt von Nadja Drusenheimer aus Remscheid Göttingen 2009 D 7 Referent: Prof. Dr. med Dr. h.c. W. Engel Korreferentin: Prof. Dr. S. Hoyer-Fender Tag der mündlichen Prüfung: Table of Contents I TABLE OF CONTENTS TABLE OF CONTENTS ----------------------------------------------------------------------- I ABBREVIATIONS ----------------------------------------------------------------------------- V 1. INTRODUCTION ----------------------------------------------------------------------------1 1.1 Pafah1b1/Lis1 is an evolutionary conserved gene---------------------------------------------------------- 1 1.2 Mutations in LIS1 gene cause classical lissencephaly ----------------------------------------------------- 2 1.3 Expression and function of Lis1 ------------------------------------------------------------------------------- 3 1.4 Generation of the gene trap line L39GT/GT ------------------------------------------------------------------- 6 1.5 Analysis of the gene trap line L39GT/GT----------------------------------------------------------------------- 7 1.6 Objectives of this study------------------------------------------------------------------------------------------ 9 2. MATERIALS AND METHODS --------------------------------------------------------- 10 2.1 Materials ----------------------------------------------------------------------------------------------------------10
    [Show full text]
  • Comprehensive Analysis Reveals Novel Gene Signature in Head and Neck Squamous Cell Carcinoma: Predicting Is Associated with Poor Prognosis in Patients
    5892 Original Article Comprehensive analysis reveals novel gene signature in head and neck squamous cell carcinoma: predicting is associated with poor prognosis in patients Yixin Sun1,2#, Quan Zhang1,2#, Lanlin Yao2#, Shuai Wang3, Zhiming Zhang1,2 1Department of Breast Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; 2School of Medicine, Xiamen University, Xiamen, China; 3State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China Contributions: (I) Conception and design: Y Sun, Q Zhang; (II) Administrative support: Z Zhang; (III) Provision of study materials or patients: Y Sun, Q Zhang; (IV) Collection and assembly of data: Y Sun, L Yao; (V) Data analysis and interpretation: Y Sun, S Wang; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. #These authors contributed equally to this work. Correspondence to: Zhiming Zhang. Department of Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, China. Email: [email protected]. Background: Head and neck squamous cell carcinoma (HNSC) remains an important public health problem, with classic risk factors being smoking and excessive alcohol consumption and usually has a poor prognosis. Therefore, it is important to explore the underlying mechanisms of tumorigenesis and screen the genes and pathways identified from such studies and their role in pathogenesis. The purpose of this study was to identify genes or signal pathways associated with the development of HNSC. Methods: In this study, we downloaded gene expression profiles of GSE53819 from the Gene Expression Omnibus (GEO) database, including 18 HNSC tissues and 18 normal tissues.
    [Show full text]
  • FMR1 Antibody (N-Term) Affinity Purified Rabbit Polyclonal Antibody (Pab) Catalog # AP6879A
    10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 FMR1 Antibody (N-term) Affinity Purified Rabbit Polyclonal Antibody (Pab) Catalog # AP6879A Specification FMR1 Antibody (N-term) - Product Information Application WB, IHC-P, FC,E Primary Accession Q06787 Reactivity Human, Mouse Host Rabbit Clonality Polyclonal Isotype Rabbit Ig Antigen Region 20-48 FMR1 Antibody (N-term) - Additional Information Gene ID 2332 Other Names Western blot analysis of FMR1 Antibody Fragile X mental retardation protein 1, (N-term) (Cat. #AP6879a) in mouse lung FMRP, Protein FMR-1, FMR1 tissue lysates (35ug/lane). FMR1 (arrow) was detected using the purified Pab. Target/Specificity This FMR1 antibody is generated from rabbits immunized with a KLH conjugated synthetic peptide between 20-48 amino acids from the N-terminal region of human FMR1. Dilution WB~~1:1000 IHC-P~~1:50~100 FC~~1:10~50 Format Purified polyclonal antibody supplied in PBS with 0.09% (W/V) sodium azide. This antibody is purified through a protein A Formalin-fixed and paraffin-embedded column, followed by peptide affinity human brain tissue reacted with FMR1 purification. Antibody (N-term), which was peroxidase-conjugated to the secondary Storage antibody, followed by DAB staining. This data Maintain refrigerated at 2-8°C for up to 2 demonstrates the use of this antibody for weeks. For long term storage store at -20°C immunohistochemistry; clinical relevance has in small aliquots to prevent freeze-thaw not been evaluated. cycles. Precautions FMR1 Antibody (N-term) is for research use only and not for use in diagnostic or therapeutic procedures.
    [Show full text]
  • The Pdx1 Bound Swi/Snf Chromatin Remodeling Complex Regulates Pancreatic Progenitor Cell Proliferation and Mature Islet Β Cell
    Page 1 of 125 Diabetes The Pdx1 bound Swi/Snf chromatin remodeling complex regulates pancreatic progenitor cell proliferation and mature islet β cell function Jason M. Spaeth1,2, Jin-Hua Liu1, Daniel Peters3, Min Guo1, Anna B. Osipovich1, Fardin Mohammadi3, Nilotpal Roy4, Anil Bhushan4, Mark A. Magnuson1, Matthias Hebrok4, Christopher V. E. Wright3, Roland Stein1,5 1 Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 2 Present address: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 3 Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 4 Diabetes Center, Department of Medicine, UCSF, San Francisco, California 5 Corresponding author: [email protected]; (615)322-7026 1 Diabetes Publish Ahead of Print, published online June 14, 2019 Diabetes Page 2 of 125 Abstract Transcription factors positively and/or negatively impact gene expression by recruiting coregulatory factors, which interact through protein-protein binding. Here we demonstrate that mouse pancreas size and islet β cell function are controlled by the ATP-dependent Swi/Snf chromatin remodeling coregulatory complex that physically associates with Pdx1, a diabetes- linked transcription factor essential to pancreatic morphogenesis and adult islet-cell function and maintenance. Early embryonic deletion of just the Swi/Snf Brg1 ATPase subunit reduced multipotent pancreatic progenitor cell proliferation and resulted in pancreas hypoplasia. In contrast, removal of both Swi/Snf ATPase subunits, Brg1 and Brm, was necessary to compromise adult islet β cell activity, which included whole animal glucose intolerance, hyperglycemia and impaired insulin secretion. Notably, lineage-tracing analysis revealed Swi/Snf-deficient β cells lost the ability to produce the mRNAs for insulin and other key metabolic genes without effecting the expression of many essential islet-enriched transcription factors.
    [Show full text]
  • Telomere-To-Telomere Assembly of a Complete Human X Chromosome
    Article Telomere-to-telomere assembly of a complete human X chromosome https://doi.org/10.1038/s41586-020-2547-7 Karen H. Miga1,24 ✉, Sergey Koren2,24, Arang Rhie2, Mitchell R. Vollger3, Ariel Gershman4, Andrey Bzikadze5, Shelise Brooks6, Edmund Howe7, David Porubsky3, Glennis A. Logsdon3, Received: 30 July 2019 Valerie A. Schneider8, Tamara Potapova7, Jonathan Wood9, William Chow9, Joel Armstrong1, Accepted: 29 May 2020 Jeanne Fredrickson10, Evgenia Pak11, Kristof Tigyi1, Milinn Kremitzki12, Christopher Markovic12, Valerie Maduro13, Amalia Dutra11, Gerard G. Bouffard6, Alexander M. Chang2, Published online: 14 July 2020 Nancy F. Hansen14, Amy B. Wilfert3, Françoise Thibaud-Nissen8, Anthony D. Schmitt15, Open access Jon-Matthew Belton15, Siddarth Selvaraj15, Megan Y. Dennis16, Daniela C. Soto16, Ruta Sahasrabudhe17, Gulhan Kaya16, Josh Quick18, Nicholas J. Loman18, Nadine Holmes19, Check for updates Matthew Loose19, Urvashi Surti20, Rosa ana Risques10, Tina A. Graves Lindsay12, Robert Fulton12, Ira Hall12, Benedict Paten1, Kerstin Howe9, Winston Timp4, Alice Young6, James C. Mullikin6, Pavel A. Pevzner21, Jennifer L. Gerton7, Beth A. Sullivan22, Evan E. Eichler3,23 & Adam M. Phillippy2 ✉ After two decades of improvements, the current human reference genome (GRCh38) is the most accurate and complete vertebrate genome ever produced. However, no single chromosome has been fnished end to end, and hundreds of unresolved gaps persist1,2. Here we present a human genome assembly that surpasses the continuity of GRCh382, along with a gapless, telomere-to-telomere assembly of a human chromosome. This was enabled by high-coverage, ultra-long-read nanopore sequencing of the complete hydatidiform mole CHM13 genome, combined with complementary technologies for quality improvement and validation.
    [Show full text]
  • Supplemental Table 3 Two-Class Paired Significance Analysis of Microarrays Comparing Gene Expression Between Paired
    Supplemental Table 3 Two‐class paired Significance Analysis of Microarrays comparing gene expression between paired pre‐ and post‐transplant kidneys biopsies (N=8). Entrez Fold q‐value Probe Set ID Gene Symbol Unigene Name Score Gene ID Difference (%) Probe sets higher expressed in post‐transplant biopsies in paired analysis (N=1871) 218870_at 55843 ARHGAP15 Rho GTPase activating protein 15 7,01 3,99 0,00 205304_s_at 3764 KCNJ8 potassium inwardly‐rectifying channel, subfamily J, member 8 6,30 4,50 0,00 1563649_at ‐‐ ‐‐ ‐‐ 6,24 3,51 0,00 1567913_at 541466 CT45‐1 cancer/testis antigen CT45‐1 5,90 4,21 0,00 203932_at 3109 HLA‐DMB major histocompatibility complex, class II, DM beta 5,83 3,20 0,00 204606_at 6366 CCL21 chemokine (C‐C motif) ligand 21 5,82 10,42 0,00 205898_at 1524 CX3CR1 chemokine (C‐X3‐C motif) receptor 1 5,74 8,50 0,00 205303_at 3764 KCNJ8 potassium inwardly‐rectifying channel, subfamily J, member 8 5,68 6,87 0,00 226841_at 219972 MPEG1 macrophage expressed gene 1 5,59 3,76 0,00 203923_s_at 1536 CYBB cytochrome b‐245, beta polypeptide (chronic granulomatous disease) 5,58 4,70 0,00 210135_s_at 6474 SHOX2 short stature homeobox 2 5,53 5,58 0,00 1562642_at ‐‐ ‐‐ ‐‐ 5,42 5,03 0,00 242605_at 1634 DCN decorin 5,23 3,92 0,00 228750_at ‐‐ ‐‐ ‐‐ 5,21 7,22 0,00 collagen, type III, alpha 1 (Ehlers‐Danlos syndrome type IV, autosomal 201852_x_at 1281 COL3A1 dominant) 5,10 8,46 0,00 3493///3 IGHA1///IGHA immunoglobulin heavy constant alpha 1///immunoglobulin heavy 217022_s_at 494 2 constant alpha 2 (A2m marker) 5,07 9,53 0,00 1 202311_s_at
    [Show full text]
  • Human Leucine-Rich Repeat Proteins: a Genome-Wide Bioinformatic Categorization and Functional Analysis in Innate Immunity
    Human leucine-rich repeat proteins: a genome-wide bioinformatic categorization and functional analysis in innate immunity Aylwin C. Y. Nga,b,1, Jason M. Eisenberga,b,1, Robert J. W. Heatha, Alan Huetta, Cory M. Robinsonc, Gerard J. Nauc, and Ramnik J. Xaviera,b,2 aCenter for Computational and Integrative Biology, and Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; bThe Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142; and cMicrobiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 Edited by Jeffrey I. Gordon, Washington University School of Medicine, St. Louis, MO, and approved June 11, 2010 (received for review February 17, 2010) In innate immune sensing, the detection of pathogen-associated proteins have been implicated in human diseases to date, notably molecular patterns by recognition receptors typically involve polymorphisms in NOD2 in Crohn disease (8, 9), CIITA in leucine-rich repeats (LRRs). We provide a categorization of 375 rheumatoid arthritis and multiple sclerosis (10), and TLR5 in human LRR-containing proteins, almost half of which lack other Legionnaire disease (11). identifiable functional domains. We clustered human LRR proteins Most LRR domains consist of a chain of between 2 and 45 by first assigning LRRs to LRR classes and then grouping the proteins LRRs (12). Each repeat in turn is typically 20 to 30 residues long based on these class assignments, revealing several of the resulting and can be divided into a highly conserved segment (HCS) fol- protein groups containing a large number of proteins with certain lowed by a variable segment (VS).
    [Show full text]
  • The Drosophila TART Transposon Manipulates the Pirna Pathway As a Counter-Defense 2 Strategy to Limit Host Silencing 3 4 Christopher E
    bioRxiv preprint doi: https://doi.org/10.1101/2020.02.20.957324; this version posted February 20, 2020. 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. 1 The Drosophila TART transposon manipulates the piRNA pathway as a counter-defense 2 strategy to limit host silencing 3 4 Christopher E. Ellison, Meenakshi S. Kagda*, Weihuan Cao 5 Department of Genetics, Human Genetics Institute of New Jersey, Rutgers, The State University of 6 New Jersey, Piscataway, New Jersey 7 8 *Current Affiliation: Department of Genetics, Stanford University, Stanford, California 9 10 Corresponding author: 11 Christopher E. Ellison 12 [email protected] 13 14 15 Short title: Drosophila transposon counter-defense 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.02.20.957324; this version posted February 20, 2020. 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. 1 Abstract 2 Co-evolution between transposable elements (TEs) and their hosts can be antagonistic, where TEs 3 evolve to avoid silencing and the host responds by reestablishing TE suppression, or mutualistic, where 4 TEs are co-opted to benefit their host.
    [Show full text]
  • Identification of RNA-Binding Proteins As Targetable Putative Oncogenes
    International Journal of Molecular Sciences Article Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma Jessica L. Bell 1,2,*, Sven Hagemann 1, Jessica K. Holien 3,4 , Tao Liu 2, Zsuzsanna Nagy 2,5, Johannes H. Schulte 6,7, Danny Misiak 1 and Stefan Hüttelmaier 1,* 1 Institute of Molecular Medicine, Sect. Molecular Cell Biology, Martin Luther University Halle-Wittenberg, Charles Tanford Protein Center, 06120 Halle Saale, Germany; [email protected] (S.H.); [email protected] (D.M.) 2 Children’s Cancer Institute Australia, Randwick, NSW 2031, Australia; [email protected] (T.L.); [email protected] (Z.N.) 3 St. Vincent’s Institute of Medical Research, Fitzroy, Victoria 3065, Australia; [email protected] 4 Biosciences and Food Technology, School of Science, College of Science, Engineering and Health, RMIT University, Melbourne, Victoria 3053, Australia 5 School of Women’s & Children’s Health, UNSW Sydney, Randwick, NSW 2031, Australia 6 Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany; [email protected] 7 German Consortium for Translational Cancer Research (DKTK), Partner Site Charité Berlin, 10117 Berlin, Germany * Correspondence: [email protected] (J.L.B.); [email protected] (S.H.) Received: 23 April 2020; Accepted: 14 July 2020; Published: 19 July 2020 Abstract: Neuroblastoma is a common childhood cancer with almost a third of those affected still dying, thus new therapeutic strategies need to be explored. Current experimental therapies focus mostly on inhibiting oncogenic transcription factor signalling. Although LIN28B, DICER and other RNA-binding proteins (RBPs) have reported roles in neuroblastoma development and patient outcome, the role of RBPs in neuroblastoma is relatively unstudied.
    [Show full text]