GT to AT transition at a splice donor site causes skipping of the preceding exon in phenylketonuria.
GT to AT transition at a splice donor site causes skipping of the preceding exon in phenylketonuria.
复制标题
剪接供体位点处的 GT 到 AT 的转变导致苯丙酮尿症中前一个外显子的跳跃。
DOI：
10.1093/nar/15.14.5613
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发表时间：
1987
影响因子：
14.9
通讯作者：
Woo,SL
中科院分区：
文献类型：
--
作者：
Marvit,J;DiLella,AG;Brayton,K;Ledley,FD;Robson,KJ;Woo,SL
经典型苯丙酮尿症（PKU）是一种由肝苯丙氨酸羟化酶（PAH）缺乏引起的常染色体隐性遗传性疾病。我们从PKU携带者个体中分离出几个突变PAH cDNA克隆，并表明它们包含内部116个碱基对缺失，精确对应于人类染色体PAH基因的外显子12。该缺失导致缺乏C-末端52个氨基酸的截短蛋白质的合成。使用突变PAH cDNA的基因转移和表达研究表明，删除废除PAH活性在细胞中的蛋白质不稳定的结果。为了确定缺失的分子基础，从该个体中分离出突变的染色体PAH基因，并显示在内含子12的5′剪接供体位点处含有GT→AT取代。因此，人类肝脏中剪接供体位点突变的结果是在RNA剪接期间跳过前面的轴突。
Classical Phenylketonuria (PKU) is an autosomal recessive human genetic disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH). We isolated several mutant PAH cDNA clones from a PKU carrier individual and showed that they contained an internal 116 base pair deletion, corresponding precisely to exon 12 of the human chromosomal PAH gene. The deletion causes the synthesis of a truncated protein lacking the C-terminal 52 amino acids. Gene transfer and expression studies using the mutant PAH cDNA indicated that the deletion abolishes PAH activity in the cell as a result of protein instability. To determine the molecular basis of the deletion, the mutant chromosomal PAH gene was isolated from this individual and shown to contain a GT→AT substitution at the 5′ splice donor site of intron 12. Thus, the consequence of the splice donor site mutation in the human liver is the skipping of the preceding axon during RNA splicing.