EXPRESSION OF A MITOGEN-RESPONSIVE GENE ENCODING PROSTAGLANDIN SYNTHASE IS REGULATED BY MESSENGER-RNA SPLICING

EXPRESSION OF A MITOGEN-RESPONSIVE GENE ENCODING PROSTAGLANDIN SYNTHASE IS REGULATED BY MESSENGER-RNA SPLICING
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DOI:
10.1073/pnas.88.7.2692
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发表时间:
1991-04-01
影响因子:
11.1
通讯作者:
SIMMONS, DL
SIMMONS, DL
中科院分区:
综合性期刊1区
文献类型:
--
作者:
XIE, WL;CHIPMAN, JG;SIMMONS, DL

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劳斯肉瘤病毒在鸡胚成纤维细胞(CEF)中诱导编码603个氨基酸的蛋白质的4.1-脱氢酶mRNA(命名为CEF-147)。 蛋白质序列的分析表明,它与绵羊前列腺素G/H合酶,催化的生产中的限速步骤的酶共享59%的氨基酸同一性。 src癌基因产物诱导的前列腺素合酶与从绵羊精囊中分离克隆的蛋白质在蛋白质和mRNA水平上均存在显著差异,提示src癌基因产物诱导的前列腺素合酶可能是该酶的一种新形式。 src诱导的前列腺素合酶mRNA的一个显着特点是其在非增殖鸡胚成纤维细胞中的丰度低,而在src转化细胞中的丰度相对较高。 此外,大多数src诱导的前列腺素合酶RNA存在于非增殖细胞被发现是非功能性的,因为存在一个未剪接的内含子,从蛋白质的其余部分分离的信号肽。 在促有丝分裂刺激后,该内含子被去除,导致诱导完全剪接的CEF-147 mRNA。
Rous sarcoma virus was shown to induce in chicken embryo fibroblasts (CEF) a 4.1-kilobase mRNA (designated CEF-147) encoding a 603-amino acid protein. Analysis of the protein sequence showed that it shared 59% amino acid identity with sheep prostaglandin G/H synthase, the enzyme that catalyzes the rate-limiting steps in the production of prostaglandins. Significant differences, at both the protein and mRNA levels, existed between the src oncogene product-inducible prostaglandin synthase and the protein isolated and cloned from sheep seminal vesicle, suggesting that the src-inducible prostaglandin synthase may be a new form of the enzyme. A distinguishing feature of src-inducible prostaglandin synthase mRNA is its low abundance in nonproliferating chicken embryo fibroblasts and its relatively high abundance in src-transformed cells. Additionally, the majority of the src-inducible prostaglandin synthase RNA present in nonproliferating cells was found to be nonfunctional because of the presence of an unspliced intron that separated the signal peptide from the remainder of the protein. Upon mitogenic stimulation, this intron was removed, resulting in the induction of fully-spliced CEF-147 mRNA.