The E2 Marie Kondo and the CTLH E3 ligase clear deposited RNA binding proteins during the maternal-to-zygotic transition

  1. Michael Zavortink
  2. Lauren N Rutt
  3. Svetlana Dzitoyeva
  4. Jesslyn C Henriksen
  5. Chloe Barrington
  6. Danielle Y Bilodeau
  7. Miranda Wang
  8. Lily Xiao Xiao Chen
  9. Olivia S Rissland  Is a corresponding author
  1. University of Colorado School of Medicine, United States
  2. The Hospital for Sick Children, Canada

Abstract

The maternal-to-zygotic transition (MZT) is a conserved step in animal development, where control is passed from the maternal to the zygotic genome. Although the MZT is typically considered from its impact on the transcriptome, we previously found that three maternally deposited Drosophila RNA binding proteins (ME31B, Trailer Hitch [TRAL], and Cup) are also cleared during the MZT by unknown mechanisms. Here, we show that these proteins are degraded by the ubiquitin-proteasome system. Marie Kondo, an E2 conjugating enzyme, and the E3 CTLH ligase are required for the destruction of ME31B, TRAL, and Cup. Structure modeling of the Drosophila CTLH complex suggests that substrate recognition is different than orthologous complexes. Despite occurring hours earlier, egg activation mediates clearance of these proteins through the Pan Gu kinase, which stimulates translation of Kondo mRNA. Clearance of the maternal protein dowry thus appears to be a coordinated, but as-yet underappreciated, aspect of the MZT.

Data availability

Sequencing data have been deposited in GEO under accession code GSE140436. All data generated during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 2 and 4.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Michael Zavortink

    Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Lauren N Rutt

    Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Svetlana Dzitoyeva

    Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jesslyn C Henriksen

    Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Chloe Barrington

    Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Danielle Y Bilodeau

    Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8086-4233
  7. Miranda Wang

    Molecular Medicine Program, The Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  8. Lily Xiao Xiao Chen

    Molecular Medicine Program, The Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  9. Olivia S Rissland

    Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, United States
    For correspondence
    olivia.rissland@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2619-6019

Funding

National Institute of General Medical Sciences (R35GM128680)

  • Olivia S Rissland

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

Reviewing Editor

  1. Michael B Eisen, University of California, Berkeley, United States

Version history

  1. Received: November 23, 2019
  2. Accepted: June 23, 2020
  3. Accepted Manuscript published: June 23, 2020 (version 1)
  4. Version of Record published: July 27, 2020 (version 2)

Copyright

© 2020, Zavortink 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.

Metrics

  • 7,288
    Page views
  • 706
    Downloads
  • 18
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Michael Zavortink
  2. Lauren N Rutt
  3. Svetlana Dzitoyeva
  4. Jesslyn C Henriksen
  5. Chloe Barrington
  6. Danielle Y Bilodeau
  7. Miranda Wang
  8. Lily Xiao Xiao Chen
  9. Olivia S Rissland
(2020)
The E2 Marie Kondo and the CTLH E3 ligase clear deposited RNA binding proteins during the maternal-to-zygotic transition
eLife 9:e53889.
https://doi.org/10.7554/eLife.53889

Further reading

    1. Chromosomes and Gene Expression
    2. Genetics and Genomics
    James T Anderson, Steven Henikoff, Kami Ahmad
    Research Article

    Spermatogenesis in the Drosophila male germline proceeds through a unique transcriptional program controlled both by germline-specific transcription factors and by testis-specific versions of core transcriptional machinery. This program includes the activation of genes on the heterochromatic Y chromosome, and reduced transcription from the X chromosome, but how expression from these sex chromosomes is regulated has not been defined. To resolve this, we profiled active chromatin features in the testes from wildtype and meiotic arrest mutants and integrate this with single-cell gene expression data from the Fly Cell Atlas. These data assign the timing of promoter activation for genes with germline-enriched expression throughout spermatogenesis, and general alterations of promoter regulation in germline cells. By profiling both active RNA polymerase II and histone modifications in isolated spermatocytes, we detail widespread patterns associated with regulation of the sex chromosomes. Our results demonstrate that the X chromosome is not enriched for silencing histone modifications, implying that sex chromosome inactivation does not occur in the Drosophila male germline. Instead, a lack of dosage compensation in spermatocytes accounts for the reduced expression from this chromosome. Finally, profiling uncovers dramatic ubiquitinylation of histone H2A and lysine-16 acetylation of histone H4 across the Y chromosome in spermatocytes that may contribute to the activation of this heterochromatic chromosome.

    1. Chromosomes and Gene Expression
    2. Developmental Biology
    Virginia L Pimmett, Mounia Lagha
    Insight

    Imaging experiments reveal the complex and dynamic nature of the transcriptional hubs associated with Notch signaling.