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The role of the NMD factor UPF3B in olfactory sensory neurons.

  • Author(s): Tan, Kun;
  • Jones, Samantha H;
  • Lake, Blue B;
  • Dumdie, Jennifer N;
  • Shum, Eleen Y;
  • Zhang, Lingjuan;
  • Chen, Song;
  • Sohni, Abhishek;
  • Pandya, Shivam;
  • Gallo, Richard L;
  • Zhang, Kun;
  • Cook-Andersen, Heidi;
  • Wilkinson, Miles F
  • et al.

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 antimicrobial 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.

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