Abstract

The UPF3B-dependent branch of the nonsense-mediated RNA decay (NMD) pathway is critical for human cognition. Here, we examined the role of UPF3B in the olfactory system. Single-cell RNA-sequencing (scRNA-seq) analysis demonstrated considerable heterogeneity of olfactory sensory neuron (OSN) cell populations in wild type (WT) mice, and revealed that UPF3B loss influences specific subsets of these cell populations. UPF3B also regulates the expression of a large cadre of anti-microbial genes in OSNs, and promotes the selection of specific olfactory receptor (Olfr) genes for expression in mature OSNs (mOSNs). RNA-seq and Ribotag analyses identified classes of mRNAs expressed and translated at different levels in WT and Upf3b-null mOSNs. Integrating multiple computational approaches, UPF3B-dependent NMD target transcripts that are candidates to mediate the functions of NMD in mOSNs were identified in vivo. Together, our data provides a valuable resource for the olfactory field and insights into the roles of NMD in vivo.

Data availability

Sequencing data have been deposited in GEO under accession code GSE146043

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

Article and author information

Author details

  1. Kun Tan

    Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Samantha H Jones

    Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Blue B Lake

    Department of Bioengineering, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8637-9044
  4. Jennifer N Dumdie

    Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Eleen Y Shum

    Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Lingjuan Zhang

    Department of Dermatology, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Song Chen

    Department of Bioengineering, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5286-3084
  8. Abhishek Sohni

    Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Shivam Pandya

    Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Richard L Gallo

    Department of Dermatology, University of California, San Diego, San Diego, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Kun Zhang

    Department of Bioengineering, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Heidi Cook-Andersen

    Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Miles F Wilkinson

    Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, United States
    For correspondence
    mfwilkinson@health.ucsd.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6416-3058

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD093846)

  • Miles F Wilkinson

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

Ethics

Animal experimentation: This study was carried out in strict accordance with the Guidelines of the Institutional Animal Care and Use Committee (IACUC) at the University of California, San Diego. The protocol was approved by the IACUC at the University of California, San Diego (permit number: S09160).

Reviewing Editor

  1. Didier YR Stainier, Max Planck Institute for Heart and Lung Research, Germany

Publication history

  1. Received: April 17, 2020
  2. Accepted: August 9, 2020
  3. Accepted Manuscript published: August 10, 2020 (version 1)
  4. Version of Record published: August 27, 2020 (version 2)

Copyright

© 2020, Tan 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. Kun Tan
  2. Samantha H Jones
  3. Blue B Lake
  4. Jennifer N Dumdie
  5. Eleen Y Shum
  6. Lingjuan Zhang
  7. Song Chen
  8. Abhishek Sohni
  9. Shivam Pandya
  10. Richard L Gallo
  11. Kun Zhang
  12. Heidi Cook-Andersen
  13. Miles F Wilkinson
(2020)
The role of the NMD factor UPF3B in olfactory sensory neurons
eLife 9:e57525.
https://doi.org/10.7554/eLife.57525

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