OPTIONAL EXON IN THE 5'-UNTRANSLATED REGION OF 3-HYDROXY-3-METHYLGLUTARYL COENZYME-A SYNTHASE GENE - CONSERVED SEQUENCE AND SPLICING PATTERN IN HUMANS AND HAMSTERS
OPTIONAL EXON IN THE 5'-UNTRANSLATED REGION OF 3-HYDROXY-3-METHYLGLUTARYL COENZYME-A SYNTHASE GENE - CONSERVED SEQUENCE AND SPLICING PATTERN IN HUMANS AND HAMSTERS
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DOI：
10.1073/pnas.84.7.1863
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发表时间：
1987-04-01
影响因子：
11.1
通讯作者：
BROWN, MS
中科院分区：
文献类型：
--
作者：
GIL, G;SMITH, JR;BROWN, MS
3-羟基-3-甲基戊二酰辅酶A合酶（羟甲基戊二酰辅酶A合酶，EC 4.1.3.5）是胆固醇、异戊烯基tRNA和其它类异戊二烯合成途径中的负调控酶。中国仓鼠羟甲基戊二酰-CoA合酶mRNA的5“-非翻译区含有位于翻译起始位点上游10个核苷酸的59个核苷酸的任选外显子。大约50%的mRNA含有该外显子，另外50%由于内含子差异剪接而缺乏该外显子。我们发现，这两个成绩单在叙利亚仓鼠的多个组织，包括大脑中的相似比例。这两种转录物在脑和肝中的相对量从出生后第0天到第75天是恒定的。羟甲基戊二酰辅酶A合酶的一个类似的选择性剪接模式，观察到在三个人体组织：培养的成纤维细胞，胎儿肾上腺，胎儿肝脏。人合酶的cDNA在对应于任选外显子的区域中与仓鼠序列具有90%的同源性。该序列含有26个核苷酸中的20个与仓鼠羟甲基戊二酰-CoA还原酶mRNA中起始AUG密码子上游紧邻的序列匹配，该酶在类异戊二烯生物合成途径中跟随合酶。这些发现提高了可选外显子在人类和仓鼠中发挥重要的保守功能作用的可能性。
3-Hydroxy-3-methylglutaryl coenzyme A synthase (hydroxymethylglutaryl-CoA synthase, EC 4.1.3.5) is a negatively regulated enzyme in the synthetic pathway for cholesterol, isopentenyl tRNA, and other isoprenoids. The 5''-untranslated region of the mRNA for Chinese hamster hydroxymethylglutaryl-CoA synthase contains an optional exon of 59 nucleotides located 10 nucleotides upstream of the translation start site. About 50% of the mRNAs contain this exon, and the other 50% lack it owing to differential intron splicing. We show that the two transcripts are found in similar ratios in multiple tissues of the Syrian hamster, including the brain. The relative amounts of the two transcripts in brain and liver are constant from day 0 to day 75 of life. A similar alternative splicing pattern for hydroxymethylglutaryl-CoA synthase was observed in three human tissues: cultured fibroblasts, fetal adrenal gland, and fetal liver. A cDNA for human synthase had 90% homology to the hamster sequence in the region corresponding to the optional exon. This sequence contains a 20 out of 26 nucleotide match with the sequence immediately upstream of the initiator AUG codon in the mRNA for hamster hydroxymethylglutaryl-CoA reductase, the enzyme that follows the synthase in the isoprenoid biosynthetic pathway. These findings raise the possibility that the optional exon plays an important, conserved functional role in humans and hamsters.