Alternate promoters and alternate splicing of human tenascin-X, a gene with 5' and 3' ends buried in other genes.

Alternate promoters and alternate splicing of human tenascin-X, a gene with 5' and 3' ends buried in other genes.
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人生腱蛋白-X 的交替启动子和交替剪接,该基因的 5 和 3 末端埋藏在其他基因中。

DOI:
10.1093/hmg/5.11.1749
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发表时间:
1996
影响因子:
3.5
通讯作者:
Miller,WL
Miller,WL
中科院分区:
生物学2区
文献类型:
--
作者:
Speek,M;Barry,F;Miller,WL

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TN-X是一种细胞外基质蛋白,其编码基因与人类白细胞抗原6p21.3上的类固醇21-羟基酶(P450c21)基因重叠。这可能是迄今为止在人类基因组中发现的最复杂的基因座,在160kb的DNA中包含13个重叠的转录单位。以往的研究确定了该基因的39个TN-X外显子的序列,编码一个12kb的开放阅读框,但该基因的启动子(S)尚未被定位。我们确定了主要的TN-X启动子和一个先前未知的5‘未翻译外显子,该外显子位于已知外显子上游10kb以上。这个启动子与TN-C启动子有很大的不同,它启动了人胎儿肾上腺和肌肉的转录,但在人NCI-H295肾上腺癌细胞中的表达是由位于更上游的另外两个启动子启动的。其中一个与最近发现的Creb相关蛋白(Creb-RP)的启动子相同,但在人肾上腺NCI-H295肿瘤细胞中,由该启动子启动的转录产物与Creb-RP的剪接方式不同,并主要保留在这些细胞的核中。通过与tenascin家族的另外两个成员TN-C和TN-R的类比,预测TN-X应该在其纤维连接蛋白样结构域进行交替剪接。RACE克隆和RNase保护实验表明没有这种替代剪接。TN-X基因的独特之处在于它的5‘和3’端都埋藏在其他基因中。
Tenascin-X (TN-X) is an extracellular matrix protein encoded by a large gene that overlaps the steroid 21-hydroxylase (P450c21) gene in the HLA locus on chromosome 6p21.3. This may be the most complex locus in the human genome identified to date, containing 13 overlapping transcription units in 160 kb of DNA. Previous studies determined the sequence of 39 TN-X exons, encoding a 12 kb open reading frame, but the promoter(s) of the gene had not been located. We identify the principal TN-X promoter and a previously unknown 5′ untranslated exon that lies more than 10 kb upstream from the previously known exons. This promoter, which is substantially different from the promoter for TN-C, initiates transcription in human fetal adrenal and muscle, but expression in human NCI-H295 adrenocortical carcinoma cells is initiated by two other promoters lying further upstream. One of these is the same as the promoter for a recently identified Creb-related protein (Creb-rp), but transcripts initiated from this promoter in human adrenal NCI-H295 tumor cells are spliced differently from Creb-rp, and are largely retained in the nuclei of these cells. By analogy with the other two members of the tenascin family, TN-C and TN-R, it has been predicted that TN-X should undergo alternate splicing in its fibronectin-like domains. RACE cloning and RNase protection experiments reveal no such alternate splicing. The TN-X gene appears to be unique in having both its 5′ and 3′ ends buried in other genes.
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发表时间: 1985-01-01
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