The mTOR signaling pathway mediates control of ribosomal protein mRNA translation in rat liver
The mTOR signaling pathway mediates control of ribosomal protein mRNA translation in rat liver
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DOI：
10.1016/j.biocel.2004.04.004
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发表时间：
2004-11-01
影响因子：
4
通讯作者：
Kimball, SR
中科院分区：
文献类型：
--
作者：
Reiter, AK;Anthony, TG;Kimball, SR
先前的研究已经表明，对禁食大鼠口服亮氨酸导致肝脏中在信使5 '端含有寡嘧啶序列（即TOP序列）的mRNA的翻译优先增加。TOP mRNA包括编码核糖体蛋白（rp）和翻译延伸因子的那些。在培养的细胞中，大量证据表明TOP mRNA的翻译受哺乳动物雷帕霉素靶蛋白（mTOR）的调节，mTOR是一种通过核糖体蛋白S6激酶（S6K1）向rpS6发出信号的蛋白激酶。然而，之前研究的结果最近受到了几份报告的挑战，这些报告表明TOP mRNA的翻译不依赖于mTOR、S6 KI和S6磷酸化。本研究的目的是评估mTOR在体内亮氨酸刺激TOP mRNA翻译中的作用。在口服亮氨酸之前，用mTOR抑制剂雷帕霉素处理禁食大鼠。发现雷帕霉素严重减弱了肝脏中通过mTOR的亮氨酸诱导的信号传导。此外，雷帕霉素阻止了给予亮氨酸的大鼠中TOP mRNA的翻译增强，如通过与多聚核糖体相关的TOP mRNA（即那些被积极翻译的mRNA）的比例降低所评估的。相反，在雷帕霉素处理的大鼠中，核糖体蛋白mRNA积累在含有单体（mRNA结合到一个核糖体）的部分中。结果表明，在体内肝脏中，mTOR依赖性信号传导对于TOP mRNA翻译的最大刺激至关重要。(C)2004爱思唯尔有限公司保留所有权利。
Previous studies have shown that oral administration of leucine to fasted rats results in a preferential increase in liver in the translation of mRNAs containing an oligopyrimidine sequence at the 5'-end of the message (i.e. a TOP sequence). TOP mRNAs include those encoding the ribosomal proteins (rp) and translation elongation factors. In cells in culture, the preponderance of evidence suggests that translation of TOP mRNAs is regulated by the mammalian target of rapamycin (mTOR), a protein kinase that signals through ribosomal protein S6 kinase (S6K1) to rpS6. However, the results of previous studies were recently challenged by several reports suggesting that translation of TOP mRNAs is independent of mTOR, S6KI, and S6 phosphorylation. The purpose of the present study was to evaluate the role of mTOR in the stimulation of TOP mRNA translation by leucine in vivo. Fasted rats were treated with the mTOR inhibitor, rapamycin, prior to oral administration of leucine. It was found that rapamycin severely attenuated leucine-induced signaling through mTOR in liver. In addition, rapamycin prevented the enhanced translation of TOP mRNAs in rats administered leucine, as assessed by a decrease in the proportion of TOP mRNAs associated with polysomes (i.e. those mRNAs being actively translated). Instead, in rapamycin-treated rats, ribosomal protein mRNAs accumulated in the fraction containing monosomes (mRNA bound to one ribosome). The results suggest that in liver in vivo, mTOR-dependent signaling is critical for maximal stimulation of TOP mRNA translation. (C) 2004 Elsevier Ltd. All rights reserved.