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    Characterization of the 5' untranslated region of α and β isoforms of the human thromboxane A² receptor (TP). Differential promoter utilization by the TP isoforms.


    Coyle, Adrian T. and Miggin, Sinead and Kinsella, B. Therese (2002) Characterization of the 5' untranslated region of α and β isoforms of the human thromboxane A² receptor (TP). Differential promoter utilization by the TP isoforms. European Journal of Biochemistry, 269. pp. 4058-4073. ISSN 0014-2956

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    Abstract

    In humans, thromboxane (TX) A² signals through two TXA² receptor (TP) isoforms, TPα and TPβ, that diverge within their carboxyl terminal cytoplasmic (C) tail regions and arise by differential splicing. The human TP gene contains three exons E1-E3; while E1 exclusively encodes 5' untranslated region (UTR) sequence, E2 and E3 represent the main coding exons. An additional noncoding exon, E1b was identified within intron 1. Additionally, the TP gene contains two promoters P1 and P2 located 5' of E1 and E1b, respectively. Herein, we investigated the molecular basis of the differential expression of the TP isoforms by characterizing the 5' UTR of the TP transcripts. While E1 and E1b were found associated with TP transcript(s), their expression was mutually exclusive. 5' rapid amplification of cDNA ends (5' RACE) established that the major transcription initiation (TI) sites were clustered between -115 and -92 within E1 and at -99 within E1b. While E1 and E1b sequences were identified on TPα transcript(s), neither existed on TPβ transcript(s). More specifically, TPα and TPβ transcripts diverged within E2 and the major TI sites for TPβ transcripts mapped to -12/-15 therein. Through genetic reporter assays, a previously unrecognized promoter, termed P3, was identified on the TP gene located immediately 5' of -12. The proximity of P3 to the TI site of TPβ suggests a role for P3 in the control of TPβ expression and implies that TPα and TPβ, in addition to being products of differential splicing, are under the transcriptional control of distinct promoters.

    Item Type: Article
    Keywords: thromboxane receptor; isoforms; splicing; promoter; 5' untranslated region;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 12644
    Identification Number: https://doi.org/10.1046/j.1432-1033.2002.03098.x
    Depositing User: Sinead Miggin
    Date Deposited: 27 Mar 2020 11:41
    Journal or Publication Title: European Journal of Biochemistry
    Publisher: Wiley-Blackwell
    Refereed: Yes
    URI:

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