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J. Biol. Chem., Vol. 278, Issue 22, 19691-19701, May 30, 2003

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Complex Transcription and Splicing of Odorant Receptor Genes^*

From the ^aInstitut für Immungenetik, Universitätsklinikum Charité, Humboldt-Universität zu Berlin, Spandauer Damm 130, 14050 Berlin, Germany, the ^dWellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom, the ^fDepartment of Pathology, Division of Immunology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom, and the ^hUrologische Klinik, Universitätsklinikum Charité, Humboldt-Universität zu Berlin, Schumannstrasse 20/21,10117 Berlin, Germany

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.

Received for publication, December 6, 2002 , and in revised form, March 3, 2003.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AJ459831–AJ459869, AJ459872, and AJ459873.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^b Supported by Volkswagen-Stiftung Grant I/72 740 (to A. Z. and J. T.).

^c These authors contributed equally to this work.

^e Supported by a studentship from the Medical Research Council.

^g Supported by a Wellcome Trust program grant.

ⁱ Supported by the Wellcome Trust.

^j Recipients of a Wellcome Trust travel grant.

^k To whom correspondence should be addressed. Tel.: 49-30-4505-53502; Fax: 49-30-4505-53953; E-mail: andreas.ziegler{at}charite.de.

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