Posttranscriptional mechanisms account for differences in steady state levels of insulin receptor messenger RNA in different cells.
Posttranscriptional mechanisms account for differences in steady state levels of insulin receptor messenger RNA in different cells.
复制标题
转录后机制解释了不同细胞中胰岛素受体信使 RNA 稳态水平的差异。
作者：
M. Tewari;D. Tewari;R. Taub
以往的研究表明，一般情况下，胰岛素受体基因在细胞内的表达水平反映了细胞表面胰岛素受体的水平。例如，胰岛素反应性组织，如肝细胞，相对于反应性较低的细胞，如成纤维细胞，表达高水平的胰岛素受体蛋白和mRNA。此外，在患有严重胰岛素抵抗和胰岛素受体水平非常低的患者（Minn1）的细胞中，研究表明胰岛素受体基因转录物几乎无法检测到。我们早期对胰岛素受体基因启动子的研究表明，不同细胞中胰岛素受体基因转录物稳态水平的差异可能是由转录介导的。在这项研究中，我们试图评估转录和转录后机制在确定各种细胞（包括minn1成纤维细胞）胰岛素受体mRNA稳态水平中的相对贡献。使用核运行试验，我们已经确定，在不同的细胞中，包括Minn1成纤维细胞，新生胰岛素受体基因转录物的水平大致相等。因此，转录差异似乎不能解释不同细胞中胰岛素受体mRNA稳态水平的巨大差异，并且没有证据支持Minn1的胰岛素受体基因等位基因存在转录缺陷。然而，胰岛素受体mRNA的转换速率在不同细胞中有显著差异，从成纤维细胞和IM9（淋巴细胞）细胞的mRNA半衰期短至2小时到HepG2（肝）细胞的8小时不等，这在一定程度上解释了观察到的稳态胰岛素受体mRNA的差异。（摘要删节250字）
Previous studies have indicated that, in general, the insulin receptor gene is expressed at a level in cells reflecting the level of insulin receptors on the cellular surface. For instance, insulin-responsive tissues, such as hepatocytes, express high levels of both insulin receptor protein and mRNA relative to less responsive cells, such as fibroblasts. Moreover, in the cells of a patient (Minn1) with severe insulin resistance and very low levels of insulin receptors, it has been shown that insulin receptor gene transcripts are virtually undetectable. Our earlier studies of the insulin receptor gene promoter suggested that the differences in the steady state level of insulin receptor gene transcripts in different cells could be transcriptionally mediated. In this study we have attempted to assess the relative contribution of transcriptional and posttranscriptional mechanisms in determining steady state levels of insulin receptor mRNA in various cells, including Minn 1 fibroblasts. Using nuclear run-on assays, we have determined that the level of nascent insulin receptor gene transcripts is roughly equal in different cells, including Minn1 fibroblasts. Therefore, transcriptional differences do not seem to account for the dramatic differences in steady state levels of insulin receptor mRNA in different cells, and there is no evidence in support of a transcriptional defect in Minn1's insulin receptor gene alleles. However, the rate of insulin receptor mRNA turnover varies significantly in different cells, ranging from an mRNA half-life of as little as 2 h in fibroblast and IM9 (lymphocytic) cells up to 8 h in HepG2 (liver) cells, and accounts in part for the observed differences in steady state insulin receptor mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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DOI：
--
发表时间：
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期刊：
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影响因子：
--
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影响因子：
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DOI：
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发表时间：
1990
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
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DOI：
10.1172/jci113739
发表时间：
1988
期刊：
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影响因子：
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