Lerner A, D'Adamio L, Diener A C, Clayton L K, Reinherz E L
Laboratory of Immunobiology, Harvard Medical School, Boston, MA 02115.
J Immunol. 1993 Sep 15;151(6):3152-62.
CD3 zeta and eta are signal-transducing components of the TCR and are derived from alternative splicing of transcripts from a single genetic locus that also encodes CD30 theta. We have isolated two murine cDNA clones that appear to result from antisense transcription through CD3 theta-specific exon 10 and CD3 eta-specific exon 9. The sequence of these clones shows no open reading frame. Northern analysis with single stranded probes confirms the existence of a ubiquitously expressed > 12-kb polyadenylated mRNA antisense to CD3 eta. A "genomic walk," which extended 32 kb distal to murine CD3 eta exon 9, provided genomic DNA containing a more 5' portion of the antisense transcript. This probe identified two murine thymic cDNA with 91% sequence homology to the human transcription factor Oct-1. Five exons of murine Oct-1 map in an antisense orientation to the CD3 zeta/eta/theta locus on the cloned genomic sequences. The murine Oct-1 cDNA and exon 9 of CD3 eta hybridize to the same > 12-kb mRNA. Similarly, human Oct-1 and previously characterized human genomic sequences homologous to murine CD3 eta exon 9 each hybridize to the same > 15-kb human mRNA. Thus, the CD3 zeta/eta/theta and Oct-1 gene loci are partially overlapping and transcribed in opposite directions. The potential functional implications of these findings are discussed.
CD3ζ和η是T细胞受体的信号转导成分，由来自单一基因座转录本的可变剪接产生，该基因座也编码CD3θ。我们分离出两个小鼠cDNA克隆，它们似乎是通过CD3θ特异性外显子10和CD3η特异性外显子9的反义转录产生的。这些克隆的序列没有开放阅读框。用单链探针进行的Northern分析证实存在一种普遍表达的大于12 kb的多聚腺苷酸化mRNA，其与CD3η呈反义关系。一次“基因组步移”，延伸至小鼠CD3η外显子9下游32 kb，获得了包含反义转录本更5'端部分的基因组DNA。该探针鉴定出两个小鼠胸腺cDNA，与人类转录因子Oct-1具有91%的序列同源性。在克隆的基因组序列上，小鼠Oct-1的五个外显子以反义方向映射到CD3ζ/η/θ基因座。小鼠Oct-1 cDNA和CD3η的外显子9与同一条大于12 kb的mRNA杂交。同样，人类Oct-1和先前鉴定的与小鼠CD3η外显子9同源的人类基因组序列各自与同一条大于15 kb的人类mRNA杂交。因此，CD3ζ/η/θ和Oct-1基因座部分重叠且转录方向相反。本文讨论了这些发现的潜在功能意义。
