The human olfactory transcriptome.
The human olfactory transcriptome.
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DOI：
10.1186/s12864-016-2960-3
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发表时间：
2016-08-11
期刊：
影响因子：
4.4
通讯作者：
Lancet D
中科院分区：
文献类型：
--
作者：
Olender T;Keydar I;Pinto JM;Tatarskyy P;Alkelai A;Chien MS;Fishilevich S;Restrepo D;Matsunami H;Gilad Y;Lancet D
嗅觉是一种多功能的感觉机制，用于检测成千上万的挥发性气味。虽然气味信号的分子基础是相对较好的理解，相当大的差距仍然在所有相关的基因产物的完整图表。为了应对这一挑战，我们将RNAseq应用于四个充分表征的人类嗅觉上皮样本，并将结果与新的和已发表的小鼠嗅觉上皮以及16个人类对照组织进行比较。我们确定了194个非嗅觉受体（OR）基因，这些基因在人类嗅觉组织中过表达。脂质运载蛋白和杀菌/渗透性增加（BPI）折叠蛋白的过表达最高，在其他物种中包括分泌的气味载体。小鼠-人类的不一致性orthopathic脂质运载蛋白的表达表明不同的哺乳动物在这个家庭的进化路径。在这些过度表达的基因中，有36个已经证实具有嗅觉功能，而有158个以前很少或根本没有这种功能的证据。后者包括GPCR、神经肽、溶质载体、转录因子和生物转化酶。它们中的许多可能间接涉及感觉功能，并且~ 70%也在小鼠嗅上皮中过表达，证实了它们的嗅觉作用。近90%的完整OR库和~ 60%的OR假基因在嗅上皮中表达，后者显示出低3倍的表达。ORs转录水平显示出1000倍的Parabolic变异，以及显着的个体间差异。我们组装了160个转录本，代表100个完整的OR基因。这些外显子包括1-4个具有相当大的可变剪接的短的5'非编码外显子和含有编码区和高度可变长度的3'非翻译区的长的最后外显子。值得注意的是，我们确定了10个OR与一个完整的开放阅读框架，但似乎无功能的转录本，这表明一个尚未报告的OR假基因化机制。OR上游区域的分析表明同源框家族转录因子结合位点的富集和特定转录因子结合位点亚家族（Olf/EBF）的一致定位。我们提供了一个概述的表达水平的OR和辅助基因在人类嗅上皮。这形成了整个OR库的转录组学视图，并揭示了大量过度表达的未表征的人类非受体基因，为未来的发现提供了平台。本文的在线版本（doi：10.1186/s12864-016-2960-3）包含补充材料，可供授权用户使用。
Olfaction is a versatile sensory mechanism for detecting thousands of volatile odorants. Although molecular basis of odorant signaling is relatively well understood considerable gaps remain in the complete charting of all relevant gene products. To address this challenge, we applied RNAseq to four well-characterized human olfactory epithelial samples and compared the results to novel and published mouse olfactory epithelium as well as 16 human control tissues. We identified 194 non-olfactory receptor (OR) genes that are overexpressed in human olfactory tissues vs. controls. The highest overexpression is seen for lipocalins and bactericidal/permeability-increasing (BPI)-fold proteins, which in other species include secreted odorant carriers. Mouse-human discordance in orthologous lipocalin expression suggests different mammalian evolutionary paths in this family. Of the overexpressed genes 36 have documented olfactory function while for 158 there is little or no previous such functional evidence. The latter group includes GPCRs, neuropeptides, solute carriers, transcription factors and biotransformation enzymes. Many of them may be indirectly implicated in sensory function, and ~70 % are over expressed also in mouse olfactory epithelium, corroborating their olfactory role. Nearly 90 % of the intact OR repertoire, and ~60 % of the OR pseudogenes are expressed in the olfactory epithelium, with the latter showing a 3-fold lower expression. ORs transcription levels show a 1000-fold inter-paralog variation, as well as significant inter-individual differences. We assembled 160 transcripts representing 100 intact OR genes. These include 1–4 short 5’ non-coding exons with considerable alternative splicing and long last exons that contain the coding region and 3’ untranslated region of highly variable length. Notably, we identified 10 ORs with an intact open reading frame but with seemingly non-functional transcripts, suggesting a yet unreported OR pseudogenization mechanism. Analysis of the OR upstream regions indicated an enrichment of the homeobox family transcription factor binding sites and a consensus localization of a specific transcription factor binding site subfamily (Olf/EBF). We provide an overview of expression levels of ORs and auxiliary genes in human olfactory epithelium. This forms a transcriptomic view of the entire OR repertoire, and reveals a large number of over-expressed uncharacterized human non-receptor genes, providing a platform for future discovery. The online version of this article (doi:10.1186/s12864-016-2960-3) contains supplementary material, which is available to authorized users.