Evolutionarily conserved regulation of immunity by the splicing factor RNP-6/PUF60

  1. Chun Kew
  2. Wenming Huang
  3. Julia Fischer
  4. Raja Ganesan
  5. Nirmal Robinson
  6. Adam Antebi  Is a corresponding author
  1. Max Planck Institute for Biology of Ageing, Germany
  2. University of Cologne, Germany
  3. University of South Australia, Australia

Abstract

Splicing is a vital cellular process that modulates important aspects of animal physiology, yet roles in regulating innate immunity are relatively unexplored. From genetic screens in C. elegans, we identified splicing factor RNP-6/PUF60 whose activity suppresses immunity, but promotes longevity, suggesting a tradeoff between these processes. Bacterial pathogen exposure affects gene expression and splicing in a rnp-6 dependent manner, and rnp-6 gain and loss-of-function activities reveal an active role in immune regulation. Another longevity promoting splicing factor, SFA-1, similarly exerts an immuno-suppressive effect, working downstream or parallel to RNP-6. RNP-6 acts through TIR-1/PMK-1/MAPK signaling to modulate immunity. The mammalian homolog, PUF60, also displays anti-inflammatory properties, and its levels swiftly decrease after bacterial infection in mammalian cells, implying a role in the host response. Altogether our findings demonstrate an evolutionarily conserved modulation of immunity by specific components of the splicing machinery.

Data availability

RNA-seq data has been deposited in GEO. Accession code GSE141097.

The following data sets were generated

Article and author information

Author details

  1. Chun Kew

    Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Cologne, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Wenming Huang

    Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Cologne, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Julia Fischer

    Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Raja Ganesan

    Cellular-Stress and Immune Response Laboratory, Centre for Cancer Biology, University of South Australia, Adelaide, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. Nirmal Robinson

    Cellular-Stress and Immune Response Laboratory, Centre for Cancer Biology, University of South Australia, Adelaide, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7361-9491
  6. Adam Antebi

    Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Cologne, Germany
    For correspondence
    antebi@age.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7241-3029

Funding

Max-Planck-Gesellschaft

  • Chun Kew
  • Wenming Huang
  • Adam Antebi

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

Reviewing Editor

  1. Bruno Lemaître, École Polytechnique Fédérale de Lausanne, Switzerland

Publication history

  1. Received: April 6, 2020
  2. Accepted: June 14, 2020
  3. Accepted Manuscript published: June 15, 2020 (version 1)
  4. Version of Record published: July 2, 2020 (version 2)

Copyright

© 2020, Kew 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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  1. Chun Kew
  2. Wenming Huang
  3. Julia Fischer
  4. Raja Ganesan
  5. Nirmal Robinson
  6. Adam Antebi
(2020)
Evolutionarily conserved regulation of immunity by the splicing factor RNP-6/PUF60
eLife 9:e57591.
https://doi.org/10.7554/eLife.57591

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