Advertisement

  • Retraction: ‘A cell cycle regulatory network controlling NF‐κB subunit activity and function’
    Benjamin Barré, Neil D Perkins
  • Genome‐wide identification of miR‐200 targets reveals a regulatory network controlling cell invasion
    1. Cameron P Bracken1,2,
    2. Xiaochun Li1,
    3. Josephine A Wright1,
    4. David Lawrence1,
    5. Katherine A Pillman1,
    6. Marika Salmanidis1,
    7. Matthew A Anderson1,
    8. B Kate Dredge3,
    9. Philip A Gregory1,2,
    10. Anna Tsykin1,
    11. Corine Neilsen1,
    12. Daniel W Thomson1,
    13. Andrew G Bert1,
    14. Joanne M Leerberg4,
    15. Alpha S Yap4,
    16. Kirk B Jensen3,
    17. Yeesim Khew‐Goodall*,1,3, and
    18. Gregory J Goodall*,1,2,3,
    1. 1Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia
    2. 2Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia
    3. 3School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA, Australia
    4. 4Division of Molecular Cell Biology, Institute for Molecular Bioscience University of Queensland, St Lucia, Brisbane, Qld, Australia
    1. * Corresponding author. Tel: +61 8 8222 3410; Fax: +61 8 8232 4092; Email: yeesim.khew-goodall{at}health.sa.gov.au

      Corresponding author. Tel: +61 8 8222 3430; Fax +61 8 8232 4092; Email: greg.goodall{at}health.sa.gov.au

    1. These authors contributed equally to the work

    miR‐200 microRNAs are involved in the maintenance of epithelial integrity. Direct, transcriptome‐wide target detection and validation identifies genes functionally grouped as regulators of Rho GTPase signaling, invadopodia formation, metalloprotease activity and cell adhesion, which together regulate cell motility, migration and cancer metastasis.

    Synopsis

    miR‐200 microRNAs are involved in the maintenance of epithelial integrity. Direct, transcriptome‐wide target detection and validation identifies genes functionally grouped as regulators of Rho GTPase signaling, invadopodia formation, metalloprotease activity and cell adhesion, which together regulate cell motility, migration and cancer metastasis.

    • The global profile of miR‐200 targets in breast cancer cells reveals a network of cytoskeletal regulators

    • miR‐200 is found to control invadopodia, focal adhesions and Rho GTPase signaling.

    • Canonical seed‐3′UTR target site interactions are dominant, but target sites in coding regions and non‐canonical interactions are also detected.

    • Target genes identified in cell lines negatively correlate with miR‐200 across human breast cancer samples as well.

    • cytoskeleton
    • HITS‐CLIP
    • invadopodia
    • microRNA
    • miR‐200
    • Received April 2, 2014.
    • Revision received June 6, 2014.
    • Accepted June 12, 2014.
    Cameron P Bracken, Xiaochun Li, Josephine A Wright, David Lawrence, Katherine A Pillman, Marika Salmanidis, Matthew A Anderson, B Kate Dredge, Philip A Gregory, Anna Tsykin, Corine Neilsen, Daniel W Thomson, Andrew G Bert, Joanne M Leerberg, Alpha S Yap, Kirk B Jensen, Yeesim Khew‐Goodall, Gregory J Goodall
  • Aberrant methylation of tRNAs links cellular stress to neuro‐developmental disorders
    1. Sandra Blanco1,
    2. Sabine Dietmann1,
    3. Joana V Flores1,
    4. Shobbir Hussain1,
    5. Claudia Kutter2,
    6. Peter Humphreys1,
    7. Margus Lukk2,
    8. Patrick Lombard1,
    9. Lucas Treps3,
    10. Martyna Popis1,
    11. Stefanie Kellner4,
    12. Sabine M Hölter5,6,
    13. Lillian Garrett5,6,
    14. Wolfgang Wurst5,6,7,
    15. Lore Becker5,8,
    16. Thomas Klopstock7,9,
    17. Helmut Fuchs5,8,
    18. Valerie Gailus‐Durner5,8,
    19. Martin Hrabĕ de Angelis5,8,
    20. Ragnhildur T Káradóttir1,
    21. Mark Helm4,
    22. Jernej Ule10,
    23. Joseph G Gleeson11,
    24. Duncan T Odom2 and
    25. Michaela Frye*,1
    1. 1Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK
    2. 2Li Ka Shing Centre, CR‐UK Cambridge Institute, University of Cambridge, Cambridge, UK
    3. 3CNRS, UMR8104, Paris, France
    4. 4Johannes Gutenberg University Mainz, Institute for Pharmacy and Biochemistry, Mainz, Germany
    5. 5German Mouse Clinic, Helmholtz Zentrum München, Neuherberg, Germany
    6. 6Institute of Developmental Genetics, Helmholtz Zentrum München, Neuherberg, Germany
    7. 7German Center for Vertigo and Balance Disorders, Munich, Germany
    8. 8Institute for Experimental Genetics, Helmholtz Zentrum München, Neuherberg, Germany
    9. 9Department of Neurology, Friedrich‐Baur‐Institute, Ludwig‐Maximilians‐University, Munich, Germany
    10. 10Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
    11. 11Laboratory of Pediatric Brain Diseases, Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA
    1. *Corresponding author. Tel: +44 1223 760230; Fax: +44 1223 760241; E‐mails: Michaela.Frye{at}cancer.org.uk; mf364{at}cam.ac.uk

    This study causally links post‐transcriptional methylation‐controlled tRNA identity and their stability to neurological disorders in human.

    Synopsis

    This study causally links post‐transcriptional methylation‐controlled tRNA identity and their stability to neurological disorders in human.

    • NSun2‐mediated tRNA methylation protects from endonucleolytic cleavage into small RNA fragments.

    • tRNA‐derived small RNA fragments are sufficient and required to induce cellular stress responses.

    • Loss of cytosine‐5 methylation in tRNAs contributes to neuro‐developmental disease through accumulation of tRNA‐derived small RNA fragments.

    • 5‐methylcytidine
    • Misu
    • NSun2
    • RNA modification
    • Received June 16, 2014.
    • Accepted June 23, 2014.

    This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    Sandra Blanco, Sabine Dietmann, Joana V Flores, Shobbir Hussain, Claudia Kutter, Peter Humphreys, Margus Lukk, Patrick Lombard, Lucas Treps, Martyna Popis, Stefanie Kellner, Sabine M Hölter, Lillian Garrett, Wolfgang Wurst, Lore Becker, Thomas Klopstock, Helmut Fuchs, Valerie Gailus‐Durner, Martin Hrabĕ de Angelis, Ragnhildur T Káradóttir, Mark Helm, Jernej Ule, Joseph G Gleeson, Duncan T Odom, Michaela Frye
  • Reduced pachytene piRNAs and translation underlie spermiogenic arrest in Maelstrom mutant mice
    1. Julio Castañeda1,24,
    2. Pavol Genzor1,2,
    3. Godfried W van der Heijden2,
    4. Ali Sarkeshik3,
    5. John R Yates III3,
    6. Nicholas T Ingolia*,25 and
    7. Alex Bortvin*,2
    1. 1Department of Biology, Johns Hopkins University, Baltimore, MD, USA
    2. 2Department of Embryology, Carnegie Institution for Science, Baltimore, MD, USA
    3. 3Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA
    4. 4Department of Pathology, Baylor College of Medicine, Houston, TX, USA
    5. 5Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA
    1. * Corresponding author. Tel: +1 510 664 7071; E‐mail: ingolia{at}berkeley.edu

      Corresponding author. Tel:+1 410 246 3034; Fax: +1 410 243 6311; E‐mail: bortvin{at}ciwemb.edu

    Loss of piRNA biogenesis factor Maelstrom leads to flagellum malformation and aberrant translational regulation, thus offering insight on a role for the elusive mammalian pachytene piRNAs.

    Synopsis

    Loss of piRNA biogenesis factor Maelstrom leads to flagellum malformation and aberrant translational regulation, thus offering insight on a role for the elusive mammalian pachytene piRNAs.

    • MAEL‐containing complexes are enriched in piRNA pathway proteins and processing intermediates of piRNA precursors and transposon RNAs.

    • Mael‐mutant mice of 129Sv/Jae genetic background exhibit terminal spermiogenic arrest due to acrosome and flagellum defects.

    • Mael is required for pachytene piRNA production.

    • Mael mutants exhibit reduced translation of almost 900 spermiogenic mRNAs including those for acrosome and flagellum proteins.

    • germ cell
    • maelstrom
    • mouse
    • piRNA
    • Piwi
    • Received September 10, 2013.
    • Revision received June 12, 2014.
    • Accepted July 2, 2014.
    Julio Castañeda, Pavol Genzor, Godfried W van der Heijden, Ali Sarkeshik, John R Yates, Nicholas T Ingolia, Alex Bortvin
  • Stop competing, start talking!
    1. Luca L Fava1 and
    2. Andreas Villunger (andreas.villunger{at}i-med.ac.at) 1
    1. 1Division of Developmental Immunology, Biocenter, Innsbruck Medical University, Innsbruck, Austria

    According to current belief, the molecular networks orchestrating cell death or exit from mitosis upon extended mitotic arrest do not interact, stubbornly executing two parallel biological programs and competing to define a stochastic decision between death and a chance for survival with uncertain destiny. However, recent findings by Diaz‐Martinez et al (2014) in this issue of The EMBO Journal now call for a reassessment of the “competing network” hypothesis.

    See also: LA Diaz‐Martinez et al

    A screen revealing coupling of apoptosis and checkpoint adaptation pathways calls for reevaluation of the competing network model for explaining the fate of cells upon extended mitotic arrest.

    Luca L Fava, Andreas Villunger
  • A positive signal prevents secretory membrane cargo from recycling between the Golgi and the ER
    1. Matteo Fossati13,
    2. Sara F Colombo1 and
    3. Nica Borgese*,1,2
    1. 1BIOMETRA Department, CNR Institute of Neuroscience, Università degli Studi di Milano, Milano, Italy
    2. 2Department of Health Science, Magna Graecia University of Catanzaro, Catanzaro, Italy
    3. 3Institute of Biology at the École Normale Supérieure (IBENS), Paris, France
    1. *Corresponding author. Tel: +3902 50316947; Fax: +3902 50317132; E‐mail: n.borgese{at}in.cnr.it

    Plasma membrane (PM)‐targeted proteins cycle back and forth between ER and Golgi. Proteins equipped with a polypeptide export signature escape the Rab6‐regulated retrograde pathway more easily, reaching the PM faster.

    Synopsis

    Plasma membrane (PM)‐targeted proteins cycle back and forth between ER and Golgi. Proteins equipped with a polypeptide export signature escape the Rab6‐regulated retrograde pathway more easily, reaching the PM faster.

    • Correctly folded membrane proteins destined to the plasma membrane may engage in recycling between the Golgi and the ER during their transport through the early secretory pathway.

    • Vesicular Stomatitis Virus Glycoprotein is prevented from entering the Golgi‐to‐ER recycling pathway due to the presence of a tyrosine and diacidic‐based ER export signal in its cytosolic tail.

    • The small GTPase Rab6 is required for the retrograde transport of signal‐deficient, surface‐directed cargo proteins.

    • Recycling of membrane cargoes within the early secretory pathway is a novel mechanism regulating the overall transport rate through the secretory pathway.

    • live cell imaging
    • Rab6
    • retrograde transport
    • secretory pathway
    • VSV glycoprotein
    • Received March 2, 2014.
    • Revision received June 17, 2014.
    • Accepted June 25, 2014.
    Matteo Fossati, Sara F Colombo, Nica Borgese
  • TLR sorting by Rab11 endosomes maintains intestinal epithelial‐microbial homeostasis
    1. Shiyan Yu1,
    2. Yingchao Nie2,
    3. Byron Knowles3,
    4. Ryotaro Sakamori1,
    5. Ewa Stypulkowski1,
    6. Chirag Patel4,
    7. Soumyashree Das1,
    8. Veronique Douard4,
    9. Ronaldo P Ferraris4,
    10. Edward M Bonder1,
    11. James R Goldenring3,
    12. Yicktung Tony Ip2 and
    13. Nan Gao*,1,5
    1. 1Department of Biological Sciences, Rutgers University, Newark, NJ, USA
    2. 2Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA
    3. 3Experimental Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
    4. 4Department of Pharmacology and Physiology, Rutgers‐New Jersey Medical School, Newark, NJ, USA
    5. 5Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
    1. *Corresponding author. Tel: +1 973 353 5523; Fax: +1 973 353 5518; E‐mail: ngao{at}andromeda.rutgers.edu

    Immunologic tolerance to intestinal microbiota depends on Rab11 endosome‐mediated control of pathogen pattern recognition receptor TLR9 processing and signaling.

    Synopsis

    Immunologic tolerance to intestinal microbiota depends on Rab11 endosome‐mediated control of pathogen pattern recognition receptor TLR9 processing and signaling.

    • Loss of Rab11a in enterocytes causes cell‐autonomous inflammatory cytokine production and crypt cell proliferation.

    • Rab11a endosomes control Toll‐like receptor distribution and processing in intestinal epithelial cells.

    • Rab11a endosome‐mediated host–microbial homeostasis is conserved in flies and mammals.

    • enterocyte
    • inflammation
    • intestinal homeostasis
    • Rab11a
    • Toll‐like receptor
    • Received January 11, 2014.
    • Revision received June 12, 2014.
    • Accepted June 13, 2014.

    This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

    Shiyan Yu, Yingchao Nie, Byron Knowles, Ryotaro Sakamori, Ewa Stypulkowski, Chirag Patel, Soumyashree Das, Veronique Douard, Ronaldo P Ferraris, Edward M Bonder, James R Goldenring, Yicktung Tony Ip, Nan Gao