IDENTIFICATION OF A COMMON NUCLEOTIDE-SEQUENCE IN THE 3'-UNTRANSLATED REGION OF MESSENGER-RNA MOLECULES SPECIFYING INFLAMMATORY MEDIATORS
IDENTIFICATION OF A COMMON NUCLEOTIDE-SEQUENCE IN THE 3'-UNTRANSLATED REGION OF MESSENGER-RNA MOLECULES SPECIFYING INFLAMMATORY MEDIATORS
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DOI：
10.1073/pnas.83.6.1670
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发表时间：
1986-03-01
影响因子：
11.1
通讯作者：
CERAMI, A
中科院分区：
文献类型：
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作者：
CAPUT, D;BEUTLER, B;CERAMI, A
最近，关于人和小鼠肿瘤坏死因子(肿瘤坏死因子；cachectin)的cDNAs序列已有报道。肿瘤坏死因子基因的编码区在人和鼠之间高度保守，在氨基酸水平上有80%的同源性。我们现在观察到33个核苷酸序列，完全由A和T残基组成，位于3‘-非翻译区，在小鼠和人的肿瘤坏死因子mRNAs中是完全保守的。由于3‘’-非翻译区通常不保守，我们推测该序列可能起到调节作用。我们在人和小鼠肿瘤坏死因子mRNAs的3‘端非翻译区，以及编码人淋巴毒素、人集落刺激因子、人和小鼠白介素1、人和大鼠纤维连接蛋白的mRNAs，以及大多数已测序的人和小鼠干扰素的mRNAs中发现了一个共有序列(TTATTTAT)。除淋巴毒素mRNAs外，所有这些mRNAs都与编码区的肿瘤坏死因子mRNAs缺乏同源性。这个共有的序列在哺乳动物的mRNA中一般是不常见的，但它出现的频率比随机因素所决定的频率更高，这表明它可能在发现它的mRNA中起着特定的调节功能。它在编码与炎症反应相关的蛋白质的mRNAs中尤其普遍。
Recently, cDNA sequences have been reported for both human and murine tumor necrosis factor (TNF; cachectin). The coding region of the TNF genes is highly conserved between man and mouse; 80% homology is apparent at the amino acid level. We now observe that 33-nucleotide sequence, comprised entirely of A and T residues and located in the 3''-untranslated region, is conserved in toto in the murine and human TNF mRNAs. Since the 3''-untranslated region is normally not conserved, we reasoned that this sequence might play a regulatory role. We identified a consensus sequence (TTATTTAT) present in the 3''-untranslated region of both human and mouse TNF mRNAs, as well as the mRNAs encoding human lymphotoxin, human colony stimulating factor, human and mouse interleukin 1, human and rat fibronectin, and most of the sequenced human and mouse interferons. All of these mRNAs, except the lymphotoxin mRNA, lack homology to the TNF mRNAs in the coding region. The consensus sequence is uncommon among mammalian mRNAs in general, but it appears with a frequency greater than chance alone would dictate, suggesting that it may serve a specific regulatory function among the mRNAs in which it is found. It is particularly prevalent among mRNAs encoding proteins related to the inflammatory response.