Channel Nuclear Pore Complex subunits are required for transposon silencing in Drosophila

  1. Marzia Munafò
  2. Victoria R Lawless
  3. Alessandro Passera
  4. Serena MacMillan
  5. Susanne Bornelöv
  6. Irmgard U Haussmann
  7. Matthias Soller
  8. Gregory J Hannon  Is a corresponding author
  9. Benjamin Czech  Is a corresponding author
  1. University of Cambridge, United Kingdom
  2. University of Birmingham, United Kingdom

Abstract

The Nuclear Pore Complex (NPC) is the principal gateway between nucleus and cytoplasm that enables exchange of macromolecular cargo. Composed of multiple copies of ~30 different nucleoporins (Nups), the NPC acts as a selective portal, interacting with factors which individually license passage of specific cargo classes. Here we show that two Nups of the inner channel, Nup54 and Nup58, are essential for transposon silencing via the PIWI-interacting RNA (piRNA) pathway in the Drosophila ovary. In ovarian follicle cells, loss of Nup54 and Nup58 results in compromised piRNA biogenesis exclusively from the flamenco locus, whereas knockdowns of other NPC subunits have widespread consequences. This provides evidence that some nucleoporins can acquire specialised roles in tissue-specific contexts. Our findings consolidate the idea that the NPC has functions beyond simply constituting a barrier to nuclear/cytoplasmic exchange, as genomic loci subjected to strong selective pressure can exploit NPC subunits to facilitate their expression.

Data availability

Sequencing data have been deposited in GEO under accession number GSE152297. Mass Spectrometry data have been deposited to the PRIDE Archive under accessions PXD019670 and PXD019671. Source data files have been provided for Figure 4.

The following data sets were generated

Article and author information

Author details

  1. Marzia Munafò

    Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2689-8432
  2. Victoria R Lawless

    Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0406-6552
  3. Alessandro Passera

    Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Serena MacMillan

    Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Susanne Bornelöv

    Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9276-9981
  6. Irmgard U Haussmann

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2764-694X
  7. Matthias Soller

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3844-0258
  8. Gregory J Hannon

    Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    greg.hannon@cruk.cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4021-3898
  9. Benjamin Czech

    Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    benjamin.czech@cruk.cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8471-0007

Funding

Cancer Research UK (Core funding (A21143))

  • Gregory J Hannon

Wellcome Trust (Investigator award (110161/Z/15/Z))

  • Gregory J Hannon

Royal Society (Wolfson Research Professor (RP130039))

  • Gregory J Hannon

Boehringer Ingelheim Fonds (PhD fellowship)

  • Marzia Munafò

Biotechnology and Biological Sciences Research Council

  • Matthias Soller

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

Reviewing Editor

  1. Karsten Weis, ETH Zurich, Switzerland

Publication history

  1. Received: January 7, 2021
  2. Accepted: April 14, 2021
  3. Accepted Manuscript published: April 15, 2021 (version 1)
  4. Version of Record published: May 19, 2021 (version 2)

Copyright

© 2021, Munafò 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. Marzia Munafò
  2. Victoria R Lawless
  3. Alessandro Passera
  4. Serena MacMillan
  5. Susanne Bornelöv
  6. Irmgard U Haussmann
  7. Matthias Soller
  8. Gregory J Hannon
  9. Benjamin Czech
(2021)
Channel Nuclear Pore Complex subunits are required for transposon silencing in Drosophila
eLife 10:e66321.
https://doi.org/10.7554/eLife.66321

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