DIFFERENTIAL 3' POLYADENYLATION OF THE HUNTINGTON DISEASE GENE RESULTS IN 2 MESSENGER-RNA SPECIES WITH VARIABLE TISSUE EXPRESSION
DIFFERENTIAL 3' POLYADENYLATION OF THE HUNTINGTON DISEASE GENE RESULTS IN 2 MESSENGER-RNA SPECIES WITH VARIABLE TISSUE EXPRESSION
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DOI：
10.1093/hmg/2.10.1541
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发表时间：
1993-10-01
影响因子：
3.5
通讯作者：
HAYDEN, MR
中科院分区：
文献类型：
--
作者：
LIN, BY;ROMMENS, JM;HAYDEN, MR
最近，已鉴定出一种在 HD 染色体上扩展的包含 CAG 三核苷酸重复的新基因 (1)。该基因通过 RNA 杂交显示可检测 10-11 kb 的单个转录物。然而，我们之前已经鉴定出三种 cDNA，它们是同一基因的一部分，已被证明可以检测两种不同的 10 kb 转录本和一种明显更大的转录本 (2, 3)。这些不同的 mRNA 种类可能是由于使用了替代转录起始位点、替代剪接或选择了不同的聚腺苷酸化位点。我们已经鉴定了跨越HD基因的cDNA克隆，包括两个（HD12和HD14），它们共享相同的蛋白质编码序列，但其3'非翻译区的大小和序列不同。 HD14 在先前发布的 3' 末端远端有 3,360 个碱基对的附加序列 (1)。 RNA 杂交表明较大的 13.7 kb 片段是人脑中的主要转录本。 HD14 特有的 cDNA 片段仅检测到较大的转录本。序列分析在 HD14 cDNA 的位置 10,326 和 13,645 处鉴定了两个不同的推定聚腺苷酸化序列。这些发现表明，观察到的两种 mRNA 起源于单个基因，并且不同的多腺苷酸化导致不同大小的转录本。人脑中较大转录本的丰度相对增加可能为广泛表达的基因发挥组织特异性作用的机制提供一些见解。
Recently a novel gene containing a CAG trinucleotide repeat that is expanded on HD chromosomes has been identified(1). This gene was shown to detect a single transcript of 10-11 kb by RNA hybridization. We have however, previously identified three cDNAs which are part of the same gene that have been shown to detect two distinct transcripts of 10 kb and one that is significantly larger(2, 3). These different mRNA species could be due to use of alternate transcription start sites, alternate splicing or selection of different polyadenylation sites. We have identified cDNA clones spanning the HD gene including two (HD12 and HD14) that share identical protein coding sequences but differ in size and sequence of their 3' untranslated region. HD14 has 3,360 base pairs of additional sequence distal to the previously published 3' end (1). RNA hybridization has revealed that the larger 13.7 kb fragment is the predominant transcript in human brain. cDNA fragments unique to HD14 detected only the larger transcript. Sequence analysis identified two different putative polyadenylation sequences at position 10,326 and 13,645 of the HD14 cDNA. These findings indicate that the two observed mRNA species originate from a single gene and that differential polyadenylation leads to transcripts of different size. The relative increased abundance of the larger transcript in human brain may provide some insights into the mechanism by which a widely expressed gene may exert tissue specific effects.