1. Biochemistry and Chemical Biology
  2. Cell Biology
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The Rqc2/Tae2 subunit of the Ribosome-Associated Quality Control (RQC) complex marks ribosome-stalled nascent polypeptide chains for aggregation

  1. Ryo Yonashiro
  2. Erich B Tahara
  3. Mario H Bengtson
  4. Maria Khokhrina
  5. Holger Lorenz
  6. Kai-Chun Chen
  7. Yu Kigoshi-Tansho
  8. Jeffrey N Savas
  9. John R Yates
  10. Steve A Kay
  11. Elizabeth A Craig
  12. Axel Mogk
  13. Bernd Bukau
  14. Claudio AP Joazeiro  Is a corresponding author
  1. The Scripps Research Institute, United States
  2. University of São Paulo, Brazil
  3. University of Campinas, Brazil
  4. Zentrum für Molekulare Biologie der Universität Heidelberg, Germany
  5. Northwestern University, United States
  6. University of Wisconsin - Madison, United States
Research Article
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Cite this article as: eLife 2016;5:e11794 doi: 10.7554/eLife.11794

Abstract

Ribosome stalling during translation can be harmful, and is surveyed by a conserved quality control pathway that targets the associated mRNA and nascent polypeptide chain (NC). In this pathway, the ribosome-associated quality control (RQC) complex promotes the ubiquitylation and degradation of NCs remaining stalled in the 60S subunit. NC stalling is recognized by the Rqc2/Tae2 RQC subunit, which also stabilizes binding of the E3 ligase, Listerin/Ltn1. Additionally, Rqc2 modifies stalled NCs with a carboxy-terminal, Ala- and Thr-containing extension-the 'CAT tail.' However, the function of CAT tails and fate of CAT tail-modified ('CATylated') NCs has remained unknown. Here we show that CATylation mediates NC aggregation. NC CATylation and aggregation could be observed by inactivating Ltn1 or by analyzing NCs with limited ubiquitylation potential, suggesting that inefficient targeting by Ltn1 favors the Rqc2-mediated reaction. These findings uncover a translational stalling-dependent protein aggregation mechanism, and provide evidence that proteins can become marked for aggregation.

Article and author information

Author details

  1. Ryo Yonashiro

    Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Erich B Tahara

    University of São Paulo, São Paulo, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  3. Mario H Bengtson

    University of Campinas, São Paulo, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  4. Maria Khokhrina

    Deutsches Krebsforschungszentrum, DKFZ-ZMBH Alliance, Zentrum für Molekulare Biologie der Universität Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Holger Lorenz

    Deutsches Krebsforschungszentrum, DKFZ-ZMBH Alliance, Zentrum für Molekulare Biologie der Universität Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Kai-Chun Chen

    Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Yu Kigoshi-Tansho

    Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Jeffrey N Savas

    Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. John R Yates

    Department of Chemical Physiology, The Scripps Research Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Steve A Kay

    Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Elizabeth A Craig

    Department of Biochemistry, University of Wisconsin - Madison, Wisconsin, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Axel Mogk

    Deutsches Krebsforschungszentrum, DKFZ-ZMBH Alliance, Zentrum für Molekulare Biologie der Universität Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  13. Bernd Bukau

    Deutsches Krebsforschungszentrum, DKFZ-ZMBH Alliance, Zentrum für Molekulare Biologie der Universität Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  14. Claudio AP Joazeiro

    Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United States
    For correspondence
    joazeiro@scripps.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Ivan Dikic, Goethe University Medical School, Germany

Publication history

  1. Received: September 23, 2015
  2. Accepted: March 3, 2016
  3. Accepted Manuscript published: March 4, 2016 (version 1)
  4. Version of Record published: March 14, 2016 (version 2)

Copyright

© 2016, Yonashiro 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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