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Review Article

The multiple lives of DEAD-box RNA helicase DP103/DDX20/Gemin3

Frank Curmi, Ruben J. Cauchi
Biochemical Society Transactions Mar 09, 2018, 46 (2) 329-341; DOI: 10.1042/BST20180016
Frank Curmi
Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, MaltaCentre for Molecular Medicine and Biobanking, Biomedical Sciences Building, University of Malta, Msida, Malta
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Ruben J. Cauchi
Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, MaltaCentre for Molecular Medicine and Biobanking, Biomedical Sciences Building, University of Malta, Msida, Malta
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  • For correspondence: ruben.cauchi@um.edu.mt
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Abstract

Gemin3, also known as DDX20 or DP103, is a DEAD-box RNA helicase which is involved in more than one cellular process. Though RNA unwinding has been determined in vitro, it is surprisingly not required for all of its activities in cellular metabolism. Gemin3 is an essential gene, present in Amoeba and Metazoa. The highly conserved N-terminus hosts the helicase core, formed of the helicase- and DEAD-domains, which, based on crystal structure determination, have key roles in RNA binding. The C-terminus of Gemin3 is highly divergent between species and serves as the interaction site for several accessory factors that could recruit Gemin3 to its target substrates and/or modulate its function. This review article focuses on the known roles of Gemin3, first as a core member of the survival motor neuron (SMN) complex, in small nuclear ribonucleoprotein biogenesis. Although mechanistic details are lacking, a critical function for Gemin3 in this pathway is supported by numerous in vitro and in vivo studies. Gene expression activities of Gemin3 are next underscored, mainly messenger ribonucleoprotein trafficking, gene silencing via microRNA processing, and transcriptional regulation. The involvement of Gemin3 in abnormal cell signal transduction pathways involving p53 and NF-κB is also highlighted. Finally, the clinical implications of Gemin3 deregulation are discussed including links to spinal muscular atrophy, poliomyelitis, amyotrophic lateral sclerosis, and cancer. Impressive progress made over the past two decades since the discovery of Gemin3 bodes well for further work that refines the mechanism(s) underpinning its multiple activities.

  • DEAD-box RNA helicase
  • motor neuron disease
  • RNA
  • RNP
  • SMN complex
  • survival motor neuron
  • Abbreviations

    aa,
    amino acid;
    AGO,
    Argonaute;
    ALS,
    amyotrophic lateral sclerosis;
    ATP,
    adenosine triphosphate;
    CB,
    Cajal bodies;
    EBV,
    Epstein–Barr virus;
    Egr2,
    early growth response protein 2;
    FMRP,
    fragile X mental retardation protein;
    HDAC,
    histone deacetylase;
    IKK2,
    IκB kinase 2;
    miRNA,
    microRNA;
    MMP,
    matrix metallopeptidase;
    mRNP,
    messenger ribonucleoprotein;
    PRMT5,
    protein arginine methyltransferase 5;
    RecA,
    recombinase A;
    RISC,
    RNA-induced silencing complex;
    RNAi,
    RNA interference;
    RNP,
    ribonucleoprotein;
    SF-1,
    steroidogenic factor;
    SMA,
    spinal muscular atrophy;
    SMN,
    survival motor neuron;
    snRNA,
    small nuclear ribonucleic acid;
    snRNP,
    small nuclear ribonucleoprotein;
    TAK1,
    TGF-β-activated kinase-1;
    Tgs1,
    trimethylguanosine synthase 1
    • © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
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    April 2018

    Volume: 46 Issue: 2

    Biochemical Society Transactions: 46 (2)
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    The multiple lives of DEAD-box RNA helicase DP103/DDX20/Gemin3
    Frank Curmi, Ruben J. Cauchi
    Biochemical Society Transactions Apr 2018, 46 (2) 329-341; DOI: 10.1042/BST20180016
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    The multiple lives of DEAD-box RNA helicase DP103/DDX20/Gemin3
    Frank Curmi, Ruben J. Cauchi
    Biochemical Society Transactions Apr 2018, 46 (2) 329-341; DOI: 10.1042/BST20180016

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    • Article
      • Abstract
      • Introduction
      • Structure–function relationship
      • snRNP biogenesis
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    Keywords

    DEAD-box RNA helicase
    motor neuron disease
    RNA
    RNP
    SMN complex
    survival motor neuron

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