The role of the NMD factor UPF3B in olfactory sensory neurons

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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

(2020) The NMD factor UPF3B shapes olfactory neurogenesis
NCBI Gene Expression Omnibus, GSE146043.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE146043

The following previously published data sets were used

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NCBI Gene Expression Omnibus, GSE41785.

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Article and author information

Author details

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.
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.
Blue B Lake

Department of Bioengineering, University of California, San Diego, La Jolla, United States

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The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-8637-9044
Jennifer N Chousal

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.
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.
Lingjuan Zhang

Department of Dermatology, University of California, San Diego, La Jolla, United States

Competing interests
The authors declare that no competing interests exist.
Song Chen

Department of Bioengineering, University of California, San Diego, La Jolla, United States

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The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5286-3084
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.
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.
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.
Kun Zhang

Department of Bioengineering, University of California, San Diego, La Jolla, United States

Competing interests
The authors declare that no competing interests exist.
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.
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.

"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).

Copyright

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.