Dose-dependent action of the RNA binding protein FOX-1 to relay X-Chromosome number and determine C. elegans sex

  1. Behnom Farboud
  2. Catherine S Novak
  3. Monique Nicoll
  4. Alyssa Quiogue
  5. Barbara J Meyer  Is a corresponding author
  1. Howard Hughes Medical Institute, University of California, Berkeley, United States

Abstract

We demonstrate how RNA binding protein FOX-1 functions as a dose-dependent X-signal element to communicate X-chromosome number and thereby determine nematode sex. FOX-1, an RNA recognition motif protein, triggers hermaphrodite development in XX embryos by causing non-productive alternative pre-mRNA splicing of xol-1, the master sex-determination switch gene that triggers male development in XO embryos. RNA binding experiments together with genome editing demonstrate that FOX-1 binds to multiple GCAUG and GCACG motifs in a xol-1 intron, causing intron retention or partial exon deletion, thereby eliminating male-determining XOL-1 protein. Transforming all motifs to GCAUG or GCACG permits accurate alternative splicing, demonstrating efficacy of both motifs. Mutating subsets of both motifs partially alleviates non-productive splicing. Mutating all motifs blocks it, as does transforming them to low-affinity GCUUG motifs. Combining multiple high-affinity binding sites with the two-fold change in FOX-1 concentration between XX and XO embryos achieves dose-sensitivity in splicing regulation to determine sex.

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All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Behnom Farboud

    Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Catherine S Novak

    Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Monique Nicoll

    Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Alyssa Quiogue

    Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Barbara J Meyer

    Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
    For correspondence
    bjmeyer@berkeley.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6530-4588

Funding

Howard Hughes Medical Institute (Senior Investigator Award)

  • Barbara J Meyer

National Institutes of Health (R 35 GM 131845)

  • Barbara J Meyer

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

Reviewing Editor

  1. Douglas L Black, University of California, Los Angeles, United States

Version history

  1. Received: September 10, 2020
  2. Accepted: December 23, 2020
  3. Accepted Manuscript published: December 29, 2020 (version 1)
  4. Accepted Manuscript updated: December 30, 2020 (version 2)
  5. Version of Record published: January 6, 2021 (version 3)

Copyright

© 2020, Farboud 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. Behnom Farboud
  2. Catherine S Novak
  3. Monique Nicoll
  4. Alyssa Quiogue
  5. Barbara J Meyer
(2020)
Dose-dependent action of the RNA binding protein FOX-1 to relay X-Chromosome number and determine C. elegans sex
eLife 9:e62963.
https://doi.org/10.7554/eLife.62963

Share this article

https://doi.org/10.7554/eLife.62963

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