IRES-mediated functional coupling of transcription and translation amplifies insulin receptor feedback
IRES-mediated functional coupling of transcription and translation amplifies insulin receptor feedback
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DOI：
10.1101/gad.1506407
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发表时间：
2007-01-15
影响因子：
10.5
通讯作者：
Tjian, Robert
中科院分区：
文献类型：
--
作者：
Marr, Michael T., II;D'Alessio, Joseph A.;Tjian, Robert
人们普遍认为生物体的生长速度是由营养物质的可用性调节的。控制细胞生长的一种常见机制是通过 eIF4E 结合蛋白 (4E-BP) 全局下调帽依赖性翻译。在这里，我们报告了一种新机制的证据，该机制允许真核生物协调和选择性地耦合靶基因的转录和翻译，以响应营养和生长信号级联。果蝇胰岛素样受体 (dINR) 通路结合了含有 mRNA 的 4E-BP 抗性细胞内部核糖体进入位点 (IRES)，在功能上将转录激活与细胞中的差异翻译控制耦合起来，否则细胞中的翻译会受到 4E-BP 的抑制。尽管之前已经报道过细胞 IRES 的例子，但它们在介导关键生理反应中的关键作用尚未得到充分记录。我们的研究揭示了一种整合的转录和翻译反应机制，特别依赖于细胞 IRES，该 IRES 协调负责监测营养和细胞生长条件的重要生理信号。
It is generally accepted that the growth rate of an organism is modulated by the availability of nutrients. One common mechanism to control cellular growth is through the global down-regulation of cap-dependent translation by eIF4E-binding proteins (4E-BPs). Here, we report evidence for a novel mechanism that allows eukaryotes to coordinate and selectively couple transcription and translation of target genes in response to a nutrient and growth signaling cascade. The Drosophila insulin-like receptor (dINR) pathway incorporates 4E-BP resistant cellular internal ribosome entry site (IRES) containing mRNAs, to functionally couple transcriptional activation with differential translational control in a cell that is otherwise translationally repressed by 4E-BP. Although examples of cellular IRESs have been previously reported, their critical role mediating a key physiological response has not been well documented. Our studies reveal an integrated transcriptional and translational response mechanism specifically dependent on a cellular IRES that coordinates an essential physiological signal responsible for monitoring nutrient and cell growth conditions.