The role of the NMD factor UPF3B in olfactory sensory neurons
- University of California, San Diego, United States
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
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The NMD factor UPF3B shapes olfactory neurogenesisNCBI Gene Expression Omnibus, GSE146043.
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Global Analyses of UPF1 Binding and Function Reveal Expanded Scope of Nonsense-Mediated mRNA DecayNCBI Gene Expression Omnibus, GSE41785.
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Smg1 is required for embryogenesis and regulates diverse genes via alternative splicing coupled to nonsense-mediated mRNA decayhttps://doi.org/10.1073/pnas.1007336107.
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UPF2 Is a Critical Regulator of Liver Development, Function and Regenerationhttps://doi.org/10.1371/journal.pone.0011650.
Article and author information
Author details
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.
Reviewing Editor
- Didier YR Stainier, Max Planck Institute for Heart and Lung Research, Germany
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).
Version history
- Received: April 3, 2020
- Accepted: August 9, 2020
- Accepted Manuscript published: August 10, 2020 (version 1)
- 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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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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