Control of gene expression during T cell activation: alternate regulation of mRNA transcription and mRNA stability.
Control of gene expression during T cell activation: alternate regulation of mRNA transcription and mRNA stability.
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DOI：
10.1186/1471-2164-6-75
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发表时间：
2005-05-20
期刊：
影响因子：
4.4
通讯作者：
Becker, KG
中科院分区：
文献类型：
--
作者：
Cheadle, C;Fan, JS;Cho-Chung, YS;Werner, T;Ray, J;Do, L;Gorospe, M;Becker, KG
微阵列技术对于识别基因表达模式中复杂的全局变化已经变得非常有价值。观察到的基因表达变化与共享的转录调控元件的有效相关性仍然难以令人信服地证明。这种困难的一个原因可能是由于转录和mRNA周转事件的复杂收敛，它们一起直接影响稳态mRNA水平。为了研究基因转录和mRNA稳定性调节变化对基因表达标准分析的相对贡献，我们使用了两种不同的微阵列方法，分别测量核基因转录和polyA mRNA基因表达的变化。在用PMA加离子霉素活化人Jurkat T细胞后1小时的时间过程中，从polyA mRNA（全细胞）和核连续（新转录）RNA获得基因表达谱。比较分析表明，mRNA稳定性的调节可能占该系统中polyA mRNA变化的所有测量值的50%，这是由这些基因组的核基因转录活性没有任何相应调节所推断的。显示mRNA和核连续RNA显著升高的基因被放线菌素D（ActD）预处理细胞抑制，而大量仅通过改变mRNA周转（向上和向下）调节的基因是ActD抗性的。在整个时间过程中的一致模式，观察转录和稳定性调节基因。我们建议，mRNA稳定性的调节显着有助于观察到的基因表达的变化，在响应外部刺激，高通量系统测量。
Microarray technology has become highly valuable for identifying complex global changes in gene expression patterns. The effective correlation of observed changes in gene expression with shared transcription regulatory elements remains difficult to demonstrate convincingly. One reason for this difficulty may result from the intricate convergence of both transcriptional and mRNA turnover events which, together, directly influence steady-state mRNA levels. In order to investigate the relative contribution of gene transcription and changes in mRNA stability regulation to standard analyses of gene expression, we used two distinct microarray methods which individually measure nuclear gene transcription and changes in polyA mRNA gene expression. Gene expression profiles were obtained from both polyA mRNA (whole-cell) and nuclear run-on (newly transcribed) RNA across a time course of one hour following the activation of human Jurkat T cells with PMA plus ionomycin. Comparative analysis revealed that regulation of mRNA stability may account for as much as 50% of all measurements of changes in polyA mRNA in this system, as inferred by the absence of any corresponding regulation of nuclear gene transcription activity for these groups of genes. Genes which displayed dramatic elevations in both mRNA and nuclear run-on RNA were shown to be inhibited by Actinomycin D (ActD) pre-treatment of cells while large numbers of genes regulated only through altered mRNA turnover (both up and down) were ActD-resistant. Consistent patterns across the time course were observed for both transcribed and stability-regulated genes. We propose that regulation of mRNA stability contributes significantly to the observed changes in gene expression in response to external stimuli, as measured by high throughput systems.
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