1. Microbiology and Infectious Disease
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Functional insights from a surface antigen mRNA-bound proteome

  1. Larissa Melo do Nascimento
  2. Franziska Egler
  3. Katharina Arnold
  4. Nina Papavasiliou
  5. Christine Clayton
  6. Esteban Erben  Is a corresponding author
  1. ZMBH, Germany
  2. Deutsche Krebsforschungszentrum (DKFZ), Germany
  3. DKFZ-ZMBH Alliance, Germany
  4. IIBIO - UNSAM, Argentina
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  • Cited 1
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Cite this article as: eLife 2021;10:e68136 doi: 10.7554/eLife.68136

Abstract

Trypanosoma brucei is the causative agent of human sleeping sickness. The parasites' Variant Surface Glycoprotein (VSG) enables them to evade adaptive immunity via antigenic variation. VSG comprises 10% of total cell protein and the high stability of VSG mRNA is essential for trypanosome survival. To determine how VSG mRNA stability is maintained, we used mRNA affinity purification to identify all its associated proteins. CFB2, an unconventional RNA-binding protein with an F-box domain, was specifically enriched with VSG mRNA. We demonstrate that CFB2 is essential for VSG mRNA stability, describe cis acting elements within the VSG 3'-untranslated region that regulate the interaction, identify trans-acting factors that are present in the VSG messenger ribonucleoprotein particle and mechanistically explain how CFB2 stabilizes the mRNA of this key pathogenicity factor. Beyond T. brucei, the mRNP purification approach has the potential to supply detailed biological insight into metabolism of relatively abundant mRNAs in any eukaryote.

Data availability

The RNASeq raw data is available at Array Express with the accession number E-MTAB-9700. The proteomics data are available via ProteomeXchange with identifier PXD021772.

The following data sets were generated

Article and author information

Author details

  1. Larissa Melo do Nascimento

    CC lab, ZMBH, Heidelberg, Germany
    Competing interests
    No competing interests declared.
  2. Franziska Egler

    CC lab, ZMBH, Heidelberg, Germany
    Competing interests
    No competing interests declared.
  3. Katharina Arnold

    CC lab, ZMBH, Heidelberg, Germany
    Competing interests
    No competing interests declared.
  4. Nina Papavasiliou

    Deutsche Krebsforschungszentrum (DKFZ), Heidelberg, Germany
    Competing interests
    No competing interests declared.
  5. Christine Clayton

    Zentrum fuer Molekulare Biologie der Universitaet Heidelberg, DKFZ-ZMBH Alliance, Heidelberg, Germany
    Competing interests
    Christine Clayton, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6384-0731
  6. Esteban Erben

    Molecular Parasitology, IIBIO - UNSAM, San Martín, Argentina
    For correspondence
    eerben@iib.unsam.edu.ar
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5179-7863

Funding

H2020 European Research Council (649019)

  • Nina Papavasiliou

Core Funding University of Heidelberg (ND)

  • Christine Clayton

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Dominique Soldati-Favre, University of Geneva, Switzerland

Publication history

  1. Received: March 7, 2021
  2. Accepted: March 18, 2021
  3. Accepted Manuscript published: March 30, 2021 (version 1)
  4. Version of Record published: April 16, 2021 (version 2)

Copyright

© 2021, Melo do Nascimento et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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