Complex Transcription and Splicing of Odorant Receptor Genes

Abstract

Human major histocompatibility (human leucocyte antigen (HLA)) complex-linked odorant receptor (OR) genes are among the best characterized OR genes in the human genome. In addition to their functions as odorant receptors in olfactory epithelium, they have been suggested to play a role in the fertilization process. Here, we report the first in-depth analysis of their expression and regulation within testicular tissue. Sixteen HLA-linked OR and three non-HLA-linked OR were analyzed. One OR gene (hs6M1-16, in positive transcriptional orientation) exhibited six different transcriptional start sites combined with extensive alternative splicing within the 5 -untranslated region, the coding exon, and the 3 -untranslated region. Long distance splicing, exon sharing, and premature polyadenylation were features of another three OR loci (hs6M1-18, -21, and -27, all upstream of hs6M1-16, but in negative transcriptional orientation). Determination of the transcriptional start sites of these OR genes identified a region of 81 bp with potential bi-directional transcriptional activity. The results demonstrate that HLA-linked OR genes are subject to unusually complex transcriptional regulatory mechanisms.

Variation and linkage disequilibrium within odorant receptor gene clusters linked to the human major histocompatibility complex

“…However, such observations should not be generalized, as exceptions do exist [22,23], although these were reported for birds, which, similarly to chickens, appear to lack MHC-linked OR genes [24]. A more direct role of chemoreceptors (such as OR) in reproduction is supported by the finding of their expression in mammalian testis [25][26][27][28][29][30][31], and sperm cells [30,32,33]. The products of several polymorphic HLA-linked OR genes are expressed in this tissue [29].…”

Alternative splicing produces two transcripts encoding female-biased pheromone subfamily receptors in the navel orangeworm, Amyelois transitella

“…For mammalian ORs, alternative splicing is extensive, but rarely occurs within the coding region (Volz et al, 2003;Young et al, 2003). Alternative splicing at the N-termini of ORs and mainly, gustatory receptors has been detected for Drosophila, Anopheles, Aedes, and Tribolium (Clyne et al, 2000;Hill et al, 2002;Robertson et al, 2003;Abdel-Latief, 2007;Kent et al, 2008), however, this is the first evidence of alternative splicing changing the C-terminal amino acid sequence in an OR from insects.…”

Risk for intentional violent death associated with HLA genotypes: a preliminary survey of deceased American organ donors

“…Nevertheless, Volz et al (2003) identified 350 human OR genes that have not been disrupted. Furthermore, Volz et al (2003) as well as Ehlers et al (2000) and Younger et al (2001) have examined the human HLA OR gene cluster, finding that these OR genes are very polymorphic but are subject to complex transcriptional regulation (i.e., active).…”

“…Furthermore, Volz et al (2003) as well as Ehlers et al (2000) and Younger et al (2001) have examined the human HLA OR gene cluster, finding that these OR genes are very polymorphic but are subject to complex transcriptional regulation (i.e., active). Monti-Bloch et al (1998) provided functional brain imaging data demonstrating a functional human vomeronasal organ (VNO).…”