Skip to main content

Main menu

  • Home
  • About the Journal
    • General Information
    • Scope
    • Editorial Board
    • Impact & Metrics
    • Benefits of Publishing
    • Advertising/Sponsorship
    • About the Biochemical Society
  • Current Issue
  • For Authors
    • Submit Your Paper
    • Submission Guidelines
    • Editorial Policy
    • Open Access Policy
    • Rights and Permissions
    • Biochemical Society Member Benefits
  • For Librarians
    • Subscriptions and Pricing
    • Check Your Usage
    • Terms and Conditions
      • Biochemical Journal- Terms and Conditions of Usage
    • Open Access Policy
    • FAQs for Librarians
    • Register for Free Trial
  • For Readers
    • Subscribe
    • Rights and Permissions
    • Biochemical Society Member Benefits
    • Journal Access for Biochemical Society Members
    • Request a Free Trial
  • Collections
    • Article Collections
    • Classic Articles
  • Help
    • Technical Support
    • Contact Us
  • Other Publications
    • NEW: Emerging Topics in Life Sciences
    • NEW: Neuronal Signaling
    • Clinical Science
    • Biochemical Journal
    • Biochemical Society Transactions
    • Bioscience Reports
    • Essays in Biochemistry
    • Biochemical Society Symposia
    • Cell Signalling Biology
    • Glossary of Biochemistry and Molecular Biology
    • The Biochemist
    • Biochemical Society

User menu

  • Log-in
  • Subscribe
  • Contact Us

Search

  • Advanced search
  • Other Publications
    • NEW: Emerging Topics in Life Sciences
    • NEW: Neuronal Signaling
    • Clinical Science
    • Biochemical Journal
    • Biochemical Society Transactions
    • Bioscience Reports
    • Essays in Biochemistry
    • Biochemical Society Symposia
    • Cell Signalling Biology
    • Glossary of Biochemistry and Molecular Biology
    • The Biochemist
    • Biochemical Society

Log-in

Sign-up for alerts  
  • My Cart
Biochemical Journal
Browse Archive
Advanced Search
  • Home
  • About the Journal
    • General Information
    • Scope
    • Editorial Board
    • Impact & Metrics
    • Benefits of Publishing
    • Advertising/Sponsorship
    • About the Biochemical Society
  • Current Issue
  • For Authors
    • Submit Your Paper
    • Submission Guidelines
    • Editorial Policy
    • Open Access Policy
    • Rights and Permissions
    • Biochemical Society Member Benefits
  • For Librarians
    • Subscriptions and Pricing
    • Check Your Usage
    • Terms and Conditions
    • Open Access Policy
    • FAQs for Librarians
    • Register for Free Trial
  • For Readers
    • Subscribe
    • Rights and Permissions
    • Biochemical Society Member Benefits
    • Journal Access for Biochemical Society Members
    • Request a Free Trial
  • Collections
    • Article Collections
    • Classic Articles
  • Help
    • Technical Support
    • Contact Us

Research article

Expression of an RNA glycosidase inhibits HIV-1 transactivation of transcription

Meherzad Kutky, Katalin A. Hudak
Biochemical Journal Oct 05, 2017, 474 (20) 3471-3483; DOI: 10.1042/BCJ20170353
Meherzad Kutky
Department of Biology, York University, Toronto, Ontario, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • View author's works on this site
Katalin A. Hudak
Department of Biology, York University, Toronto, Ontario, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • View author's works on this site
  • For correspondence: hudak@yorku.ca
  • Article
  • Figures
  • Info & Metrics
  • PDF
Loading

This article has a commentary. Please see:

  • RNA glycosidase and other agents target Tat to inhibit HIV-1 transcription

Abstract

HIV-1 (human immunodeficiency virus) transcription is primarily controlled by the virally encoded Tat (transactivator of transcription) protein and its interaction with the viral TAR (transcription response element) RNA element. Specifically, binding of a Tat-containing complex to TAR recruits cellular factors that promote elongation of the host RNA polymerase engaging the viral DNA template. Disruption of this interaction halts viral RNA transcription. In the present study, we investigated the effect of pokeweed antiviral protein (PAP), an RNA glycosidase (EC#: 3.2.2.22) synthesized by the pokeweed plant (Phytolacca americana), on transcription of HIV-1 mRNA. We show that co-expression of PAP with a proviral clone in culture cells resulted in a Tat-dependent decrease in viral mRNA levels. PAP reduced HIV-1 transcriptional activity by inhibiting Tat protein synthesis. The effects of PAP expression on host factors AP-1 (activator protein 1), NF-κB (nuclear factor kappa-light-chain-enhancer of activated B-cells) and specificity protein 1, which modulate HIV-1 transcription by binding to the viral LTR (5′-long terminal repeat), were also investigated. Only AP-1 showed a modest JNK pathway-dependent increase in activity in the presence of PAP; however, this activation was not sufficient to significantly enhance transcription from a partial viral LTR containing AP-1 binding sites. Therefore, the primary effect of PAP on HIV-1 transcription is to reduce viral RNA synthesis by decreasing the abundance of Tat. These findings provide a mechanistic explanation for the observed decrease in viral RNAs in cells expressing PAP and contribute to our understanding of the antiviral effects of this plant protein.

  • depurination
  • HIV-1
  • pokeweed antiviral protein
  • ribosome inactiviating protein
  • RNA glycosidase
  • transactivator of transcription
  • Abbreviations

    AP-1,
    activator protein 1;
    CAT,
    chloramphenicol acetyltransferase;
    DMEM,
    Dubelco's Eagle Modified Medium;
    ERK1/2,
    extracellular signal-regulated kinase;
    FBS,
    fetal bovine serum;
    GAPDH,
    glyceraldehyde 3-phospate dehydrogenase;
    HIV-1,
    human immunodeficiency virus;
    JNK1,
    c-Jun NH2-terminal kinase 1 (JNK1);
    LTR,
    5′-long terminal repeat;
    NF-κB,
    nuclear factor kappa-light-chain-enhancer of activated B-cells;
    PAP,
    pokeweed antiviral protein;
    PKR,
    RNA-activated protein kinase;
    R region,
    repeat region;
    SP-1,
    specificity protein 1;
    TAR,
    transcription response element;
    Tat,
    transactivator of transcription;
    U3,
    untranslated 3′ region
    • © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
    View Full Text

    Log in using your username and password

    Enter your Biochemical Journal username.
    Enter the password that accompanies your username.
    Forgot your user name or password?

    Log in through your institution

    You may be able to gain access using your login credentials for your institution. Contact your library if you do not have a username and password.
    If your organization uses OpenAthens, you can log in using your OpenAthens username and password. To check if your institution is supported, please see this list. Contact your library for more details.
    Previous ArticleNext Article
    Back to top

     

     

    October 2017

    Volume: 474 Issue: 20

    Biochemical Journal: 474 (20)
    • Table of Contents
    • About the Cover
    • Index by author

    Actions

    Email

    Thank you for your interest in spreading the word about Biochemical Journal.

    NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

    Enter multiple addresses on separate lines or separate them with commas.
    Expression of an RNA glycosidase inhibits HIV-1 transactivation of transcription
    (Your Name) has forwarded a page to you from Biochemical Journal
    (Your Name) thought you would like to see this page from the Biochemical Journal web site.
    Share
    Expression of an RNA glycosidase inhibits HIV-1 transactivation of transcription
    Meherzad Kutky, Katalin A. Hudak
    Biochemical Journal Oct 2017, 474 (20) 3471-3483; DOI: 10.1042/BCJ20170353
    del.icio.us logo Digg logo Reddit logo Technorati logo Twitter logo CiteULike logo Facebook logo Mendeley logo
    Citation Tools
    Expression of an RNA glycosidase inhibits HIV-1 transactivation of transcription
    Meherzad Kutky, Katalin A. Hudak
    Biochemical Journal Oct 2017, 474 (20) 3471-3483; DOI: 10.1042/BCJ20170353

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero
    Print
    Alerts

    Please log in to add an alert for this article.

    Request Permissions
    Save to my folders

    View Full PDF

     Open in Utopia Docs
    • Tweet Widget
    • Facebook Like

    Jump To

    • Article
      • Abstract
      • Introduction
      • Materials and methods
      • Results
      • Discussion
      • Author Contribution
      • Funding
      • Competing Interests
      • Acknowledgements
      • References
    • Figures
    • Info & Metrics
    • PDF

    Keywords

    depurination
    HIV-1
    pokeweed antiviral protein
    ribosome inactiviating protein
    RNA glycosidase
    transactivator of transcription

    Related Articles

    Cited By...

    • Portland Press Homepage
    • Publish With Us
    • Advertising
    • Technical Support
    • Biochemical Journal
    • Clinical Science
    • Essays in Biochemistry
    • Emerging Topics in Life Sciences
    • Biochemical Society Transactions
    • Neuronal Signaling
    • Bioscience Reports
    • Cell Signalling Biology
    • Biochemical Society Symposia

    Portland Press Limited
    Charles Darwin House
    12 Roger Street
    London WC1N 2JU
    Tel: +44(0) 20 7685 2410
    Fax: +44(0) 20 7685 2469
    Email: editorial@portlandpress.com

    The Biochemical Society