Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine University of California, San Diego, San Diego, United States.
Department of Bioengineering, University of California, San Diego, San Diego, United States.
Elife. 2020 Aug 10;9:e57525. doi: 10.7554/eLife.57525.
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 () 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 -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.
UPF3B 依赖性无义介导的 RNA 降解 (NMD) 通路分支对人类认知至关重要。在这里，我们研究了 UPF3B 在嗅觉系统中的作用。单细胞 RNA 测序 (scRNA-seq) 分析表明，野生型 (WT) 小鼠的嗅觉感觉神经元 (OSN) 细胞群体存在相当大的异质性，并揭示 UPF3B 缺失会影响这些细胞群体的特定亚群。UPF3B 还调节 OSN 中大量抗菌基因的表达，并促进特定嗅觉受体 () 基因在成熟 OSN (mOSN) 中的表达选择。RNA-seq 和 Ribotag 分析鉴定了在 WT 和 -null mOSN 中以不同水平表达和翻译的 mRNA 类别。通过整合多种计算方法，在体内鉴定了 UPF3B 依赖性 NMD 靶转录本，它们是介导 mOSN 中 NMD 功能的候选物。总之，我们的数据为嗅觉领域提供了有价值的资源，并深入了解了 NMD 在体内的作用。
