title: The human olfactory transcriptome.
abstract: 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.
  
  
  
  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.
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. tsviya.olender@weizmann.ac.il.
authors: Tsviya
authors: T
authors: Olender
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors: Ifat
authors: I
authors: Keydar
authors: Section of Otolaryngology-Head and Neck Surgery, University of Chicago, Chicago, IL, USA.
authors: Jayant M
authors: JM
authors: Pinto
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors: Pavlo
authors: P
authors: Tatarskyy
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors: Anna
authors: A
authors: Alkelai
authors: Department of Molecular Genetics and Microbiology, Department of Neurobiology, Duke Institute for Brain Sciences, Duke University Medical Center, Durham, NC, USA.
authors: Ming-Shan
authors: MS
authors: Chien
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors: Simon
authors: S
authors: Fishilevich
authors: Department of Cell and Developmental Biology, Neuroscience Program, and Rocky Mountain Taste and Smell Center, University of Colorado School of Medicine, Aurora, CO, USA.
authors: Diego
authors: D
authors: Restrepo
authors: Department of Molecular Genetics and Microbiology, Department of Neurobiology, Duke Institute for Brain Sciences, Duke University Medical Center, Durham, NC, USA.
authors: Hiroaki
authors: H
authors: Matsunami
authors: Department of Human Genetics, University of Chicago, Chicago, IL, USA.
authors: Yoav
authors: Y
authors: Gilad
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors: Doron
authors: D
authors: Lancet
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D054834:Lipocalins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D009831:Olfactory Mucosa / Q000378:metabolism*; D010802:Phylogeny; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011544:Pseudogenes; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D018035:Receptors, Odorant / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D012903:Smell / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D001324:Autoantigens; C568077:BPIFB1 protein, human; D050556:Fatty Acid-Binding Proteins; D054834:Lipocalins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D020033:Protein Isoforms; D011506:Proteins; D012333:RNA, Messenger; D018035:Receptors, Odorant; D014157:Transcription Factors
keywords: Olfaction; Olfactory epithelium; Olfactory receptor; RNAseq