The RNA helicase UPF1 associates with mRNAs co-transcriptionally and is required for the release of mRNAs from gene loci

Abstract

UPF1 is an RNA helicase that is required for efficient nonsense-mediated mRNA decay (NMD) in eukaryotes, and the predominant view is that UPF1 mainly operates on the 3'UTRs of mRNAs that are directed for NMD in the cytoplasm. Here we offer evidence, obtained from Drosophila, that UPF1 constantly moves between the nucleus and cytoplasm by a mechanism that requires its RNA helicase activity. UPF1 is associated, genome-wide, with nascent RNAs at most of the active Pol II transcription sites and at some Pol III-transcribed genes, as demonstrated microscopically on the polytene chromosomes of salivary glands and by ChIP-seq analysis in S2 cells. Intron recognition seems to interfere with association and translocation of UPF1 on nascent pre-mRNAs, and cells depleted of UPF1 show defects in the release of mRNAs from transcription sites and mRNA export from the nucleus.

Data availability

ChIp-Seq and RNA -Seq data have been deposited in GEO under accession code GSE116808, GSE116806 and GSE116807.

The following data sets were generated

Article and author information

Author details

  1. Anand K Singh

    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:" 0000-0001-6500-6727
  2. Subhendu Roy Choudhury

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Sandip De

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Jie Zhang

    Life Sciences, University of Warwick, Coventry, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Stephen Kissane

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Vibha Dwivedi

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Preethi Ramanathan

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Marija Petric

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Luisa Orsini

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Daniel Hebenstreit

    Life Sciences, University of Warwick, Coventry, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0144-6728
  11. Saverio Brogna

    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    For correspondence
    s.brogna@bham.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7063-4381

Funding

Leverhulme Trust (RPG-2014-291)

  • Saverio Brogna

Wellcome (9340/Z/09/Z)

  • Saverio Brogna

Biotechnology and Biological Sciences Research Council (BB/M022757/1)

  • Saverio Brogna

Biotechnology and Biological Sciences Research Council (BB/M017982/1)

  • Daniel Hebenstreit

Biotechnology and Biological Sciences Research Council (BB/L006340/1)

  • Daniel Hebenstreit

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

Reviewing Editor

  1. Robert H Singer, Albert Einstein College of Medicine, United States

Version history

  1. Received: August 26, 2018
  2. Accepted: March 22, 2019
  3. Accepted Manuscript published: March 25, 2019 (version 1)
  4. Version of Record published: April 3, 2019 (version 2)

Copyright

© 2019, Singh 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. Anand K Singh
  2. Subhendu Roy Choudhury
  3. Sandip De
  4. Jie Zhang
  5. Stephen Kissane
  6. Vibha Dwivedi
  7. Preethi Ramanathan
  8. Marija Petric
  9. Luisa Orsini
  10. Daniel Hebenstreit
  11. Saverio Brogna
(2019)
The RNA helicase UPF1 associates with mRNAs co-transcriptionally and is required for the release of mRNAs from gene loci
eLife 8:e41444.
https://doi.org/10.7554/eLife.41444

Share this article

https://doi.org/10.7554/eLife.41444

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