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  • Orphan enzyme cuts down on sugar
    1. Siniša Urban (surban{at}jhmi.edu) 1
    1. 1Howard Hughes Medical Institute, Department of Molecular Biology & Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    The reclusive enzymes that catalyze proteolysis inside the cell membrane are among the most widespread in nature, yet most remain ‘orphans’ whose cellular functions are poorly understood. Now, Voss et al identify Golgi‐resident glycosyltransferases and glycosidases as substrates for the presenilin‐like protease SPPL3. Shedding of these glycan‐modifying enzymes from the membrane down‐regulates global protein N‐glycosylation.

    See also: M Voss et al

    The presenilin‐like protease SPPL3 cleaves Golgi‐resident glycosyltransferases and glycosidases to regulate global protein N‐glycosylation.

    Siniša Urban
  • Making ends meet: a role of RNA ligase RTCB in unfolded protein response
    1. Witold Filipowicz (witold.filipowicz{at}fmi.ch) 1
    1. 1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland

    The unfolded protein response (UPR) monitors the protein folding capacity of the endoplasmic reticulum. One of the UPR branches includes an unusual cytoplasmic splicing reaction leading to removal of an intron from an mRNA encoding a key UPR transcription factor. The cleavage step of the process is well characterized in both yeast and animals, but the animal enzyme responsible for exon ligation has remained a mystery. Recent reports, including a paper in this issue of The EMBO Journal, identify RTCB as the RNA ligase operating during UPR in mammals and C. elegans.

    See also: J Jurkin et al,

    SG Kosmaczewski et al and

    Y Lu et al

    Recent studies show that RTCB not only processes intron‐containing tRNAs, but also splices XBP1, a key regulator of UPR that is also important for priming specific cells for high secretory activity such as plasma cells.

    Witold Filipowicz
  • GRIM REAPER peptide binds to receptor kinase PRK5 to trigger cell death in Arabidopsis
    1. Michael Wrzaczek*,1,,
    2. Julia P Vainonen1,,
    3. Simon Stael2,3,4,5,
    4. Liana Tsiatsiani2,3,4,510,
    5. Hanna Help‐Rinta‐Rahko1,6,
    6. Adrien Gauthier1,
    7. David Kaufholdt111,
    8. Benjamin Bollhöner7,
    9. Airi Lamminmäki1,
    10. An Staes4,5,
    11. Kris Gevaert4,5,
    12. Hannele Tuominen7,
    13. Frank Van Breusegem2,3,
    14. Ykä Helariutta1,6,8 and
    15. Jaakko Kangasjärvi*,1,9
    1. 1Plant Biology, Department of Biosciences University of Helsinki, Helsinki, Finland
    2. 2Department of Plant Systems Biology, VIB, Ghent, Belgium
    3. 3Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium
    4. 4Department of Medical Protein Research, VIB, Ghent, Belgium
    5. 5Department of Biochemistry, Ghent University, Ghent, Belgium
    6. 6Institute of Biotechnology, University of Helsinki, Helsinki, Finland
    7. 7Umeå Plant Science Centre, Department of Plant Physiology, Umeå University, Umeå, Sweden
    8. 8The Sainsbury Laboratory, University of Cambridge, Cambridge, UK
    9. 9Distinguished Scientist Fellowship Program, College of Science, King Saud University, Riyadh, Saudi Arabia
    10. 10Biomolecular Mass Spectrometry and Proteomics, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Centre for Biomolecular Research Utrecht University, Utrecht, The Netherlands
    11. 11 Institute of Plant Biology, Braunschweig University of Technology, Braunschweig, Germany
    1. * Corresponding author. Tel: +358 2 941 57773; Fax: +358 2 941 59552; E‐mail: michael.wrzaczek{at}helsinki.fi

      Corresponding author. Tel: +358 2 941 59444; Fax: +358 2 941 59552; E‐mail: jaakko.kangasjarvi{at}helsinki.fi

    1. These authors contributed equally to this work

    In plants, ROS‐induced cell death requires Metacaspase‐9‐mediated processing of secreted protein GRIM REAPER to produce the peptide ligand for PRK5.

    Synopsis

    In plants, ROS‐induced cell death requires Metacaspase‐9‐mediated processing of secreted protein GRIM REAPER to produce the peptide ligand for PRK5.

    • Secreted protein GRIM REAPER is processed by Metacaspase‐9, resulting in a small peptide.

    • The peptide binds to the extracellular domain of the leucine‐rich repeat receptor‐like protein kinase PRK5.

    • PRK5 has no kinase activity, but acts as a peptide receptor in vivo.

    • Metacaspase‐9 and PRK5 are required for cell death induction by GRIM REAPER.

    • ligand
    • protease
    • receptor‐like kinase
    • secreted protein
    • Received March 25, 2014.
    • Revision received October 20, 2014.
    • Accepted October 21, 2014.
    Michael Wrzaczek, Julia P Vainonen, Simon Stael, Liana Tsiatsiani, Hanna Help‐Rinta‐Rahko, Adrien Gauthier, David Kaufholdt, Benjamin Bollhöner, Airi Lamminmäki, An Staes, Kris Gevaert, Hannele Tuominen, Frank Van Breusegem, Ykä Helariutta, Jaakko Kangasjärvi
  • Dusp5 negatively regulates IL‐33‐mediated eosinophil survival and function
    1. Derek A Holmes1,
    2. Jung‐Hua Yeh13,
    3. Donghong Yan2,
    4. Min Xu2 and
    5. Andrew C Chan*,1
    1. 1Department of Immunology, Genentech, Inc., South San Francisco, CA, USA
    2. 2Department of Translational Immunology, Genentech, Inc., South San Francisco, CA, USA
    3. 3Universite d'Alx‐Marseille, Marseille, France
    1. *Corresponding author. Tel: +1 650 225 8104; E‐mail: acc{at}gene.com

    DUSP5 modulates IL‐33‐mediated survival signals in eosinophils by regulating the activation of ERK1/2 and controlling BCL‐XL expression and function.

    Synopsis

    IL‐33 plays an important role in allergic diseases and fibrosis through activation of NF‐κB and mitogen‐activated protein kinase (MAPK) pathways. DUSP5, a dual‐specificity phosphatase, is significantly upregulated following IL‐33 stimulation and attenuates eosinophil functions and survival.

    • DUSP5 is a negative regulator of IL‐33 signaling.

    • DUSP5 modulates ERK, but not NF‐κB, activation to regulate pro‐inflammatory cytokines and eosinophil survival, the latter through a MEK/BCL‐XL pathway.

    • Dusp5−/− eosinophils are hyperactivated and have prolonged survival following helminthic infection or following IL‐33 administration.

    • BCL‐XL
    • eosinophil survival
    • dual‐specificity phosphatase 5
    • Received July 6, 2014.
    • Revision received October 3, 2014.
    • Accepted October 14, 2014.
    Derek A Holmes, Jung‐Hua Yeh, Donghong Yan, Min Xu, Andrew C Chan
  • Fission yeast Cactin restricts telomere transcription and elongation by controlling Rap1 levels
    1. Luca E Lorenzi1,
    2. Amadou Bah1,
    3. Harry Wischnewski1,
    4. Vadim Shchepachev1,
    5. Charlotte Soneson2,
    6. Marco Santagostino3 and
    7. Claus M Azzalin*,1
    1. 1Institute of Biochemistry (IBC) Eidgenössische Technische Hochschule Zürich (ETHZ), Zürich, Switzerland
    2. 2Bioinformatics Core Facility, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland
    3. 3Dipartimento di Biologia e Biotecnologie “L. Spallanzani”, Università degli Studi di Pavia, Pavia, Italy
    1. *Corresponding author. Tel: +41 44 633 4410; Fax: +41 44 632 1298; E‐mail: claus.azzalin{at}bc.biol.ethz.ch

    Cactin emerges from a genomewide screen for factors controlling telomeric transcription, regulating Rap1 expression both on the level of splicing efficiency and protein stability.

    Synopsis

    Cactin emerges from a genomewide screen for factors controlling telomeric transcription, regulating Rap1 expression both on the level of splicing efficiency and protein stability.

    • Fission yeast Cay1 promotes Rap1 pre‐mRNA splicing and protein stability.

    • Reduced Rap1 levels in cay1∆ cells lead to accumulation of acetylated H3K9 at telomeres, telomere desilencing, and telomere elongation.

    • Abnormal telomeres in cay1∆ cells cause chromosomal aberrations in the cold.

    • cay1∆ cells accumulate unprocessed retrotransposon Tf2 transcripts independently of Rap1.

    • Cactin
    • fission yeast
    • heterochromatin
    • telomeres
    • TERRA
    • Received July 18, 2014.
    • Revision received October 19, 2014.
    • Accepted October 20, 2014.
    Luca E Lorenzi, Amadou Bah, Harry Wischnewski, Vadim Shchepachev, Charlotte Soneson, Marco Santagostino, Claus M Azzalin
  • Burning down the house: IRF7 makes the difference for microglia
    1. Nora Hagemeyer1 and
    2. Marco Prinz (marco.prinz{at}uniklinik-freiburg.de) 1,2
    1. 1Institute of Neuropathology, University of Freiburg, Freiburg, Germany
    2. 2BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany

    The endogenous microenvironment of the brain is an essential watchdog to guard over myeloid cell function during diseases. Limiting inflammatory reactions of activated microglia and blood‐derived monocytes is a key prerequisite for the resolution of tissue insults. So far, however, it was unknown why monocytes but not microglia are able to shift to an anti‐inflammatory state during inflammation. In this issue of The EMBO Journal, Cohen and colleagues identified the molecular switch underlying this fundamental functional change. The authors found that the transforming growth factor‐β1 (TGFβ1) prevents activated microglia to switch to an anti‐inflammatory state by regulating the expression of Irf7.

    See also: M Cohen et al

    Tissue‐specific environmental factors determine the fate of resident myeloid‐derived cells, affecting the resolution of tissue injury in the brain.

    Nora Hagemeyer, Marco Prinz
  • TDP‐1, the Caenorhabditis elegans ortholog of TDP‐43, limits the accumulation of double‐stranded RNA
    1. Tassa K Saldi*,1,
    2. Peter EA Ash2,
    3. Gavin Wilson3,4,
    4. Patrick Gonzales5,
    5. Alfonso Garrido‐Lecca1,
    6. Christine M Roberts5,
    7. Vishantie Dostal5,
    8. Tania F Gendron2,
    9. Lincoln D Stein3,
    10. Thomas Blumenthal1,
    11. Leonard Petrucelli2 and
    12. Christopher D Link5,6
    1. 1Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, USA
    2. 2Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
    3. 3Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
    4. 4Informatics and Biocomputing Platform, Ontario Institute for Cancer Research, Toronto, ON, Canada
    5. 5Institute for Behavioral Genetics University of Colorado, Boulder, CO, USA
    6. 6Integrative Physiology, University of Colorado, Boulder, CO, USA
    1. *Corresponding author. Tel: +1 303 492 0340; E‐mail: tassa.saldi{at}colorado.edu

    Mutations in RNA‐binding protein TDP‐43 are linked to ALS. This study reports that the worm homolog of TDP‐43, TDP‐1, limits the accumulation of double‐stranded RNAs, offering insight on the potential contribution of TDP‐43/TDP‐1 to disease onset.

    Synopsis

    Mutations in RNA‐binding protein TDP‐43 are linked to ALS. This study reports that the worm homolog of TDP‐43, TDP‐1, limits the accumulation of double‐stranded RNAs, offering insight on the potential contribution of TDP‐43/TDP‐1 to disease onset.

    • TDP‐1 acts co‐transcriptionally to limit the accumulation of dsRNA

    • TDP‐1 limits A‐to‐I RNA editing

    • TDP‐1 maintains chemotaxis by limiting the action of RNA interference

    • Knockdown of TDP‐43 in human cells leads to an increase in dsRNA, potentially inducing an interferon response

    • Human TDP‐43 can act as an RNA chaperone in vitro

    • neurodegeneration
    • RNA editing
    • RNA structure
    • splicing
    • Received April 18, 2014.
    • Revision received August 6, 2014.
    • Accepted September 4, 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.

    Tassa K Saldi, Peter EA Ash, Gavin Wilson, Patrick Gonzales, Alfonso Garrido‐Lecca, Christine M Roberts, Vishantie Dostal, Tania F Gendron, Lincoln D Stein, Thomas Blumenthal, Leonard Petrucelli, Christopher D Link