A common mechanism of stage-regulated gene expression in Leishmania mediated by a conserved 3′-untranslated region element
A common mechanism of stage-regulated gene expression in Leishmania mediated by a conserved 3′-untranslated region element
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DOI：
10.1074/jbc.m200500200
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发表时间：
2002-05-31
影响因子：
4.8
通讯作者：
Papadopoulou, B
中科院分区：
文献类型：
--
作者：
Boucher, N;Wu, Y;Papadopoulou, B
锥虫原虫mRNA水平的发育调控是在转录后决定的，通常涉及位于mRNAs的3‘-非翻译区(3’-UTR)的序列。我们以前已经在利什曼原虫中发现了一个编码无粘蛋白表面蛋白的发育调控基因家族，并表明无粘蛋白mRNA的阶段特异性积累是由3‘-UTR区内的序列介导的。在此，我们在amastin 3‘-UTR中发现了一个450个核苷酸的区域，它可以通过一种新的机制来促进无鞭毛体特异性基因的表达，这种新机制在不增加mRNA稳定性的情况下增加了mRNA的翻译。值得注意的是，这个450-NT 3‘-UTR元件在几个利什曼原虫的大量mRNAs中高度保守。在这里，我们证明了其中几个mRNAs在寄生虫的无鞭毛体细胞内阶段有差异表达，并且其3‘-UTRs中的450-nt保守元件负责阶段特异性的基因调控。我们认为，450-nt保守元件不同于迄今发现的任何其他调节元件，是利什曼原虫阶段调控基因表达的共同机制的一部分，该机制调节mRNA翻译以响应细胞内压力。
Developmental regulation of mRNA levels in trypanosomatid protozoa is determined post-transcriptionally and often involves sequences located in the 3'-untranslated regions (3'-UTR) of the mRNAs. We have previously identified a developmentally regulated gene family in Leishmania encoding the amastin surface proteins and showed that stage-specific accumulation of the amastin mRNA is mediated by sequences within the 3'-UTR. Here we identified a 450-nt region within the amastin 3'-UTR that can confer amastigote-specific gene expression by a novel mechanism that increases mRNA translation without an increase in mRNA stability. Remarkably, this 450-nt 3'-UTR element is highly conserved among a large number of Leishmania mRNAs in several Leishmania species. Here we show that several of these mRNAs are differentially expressed in the intracellular amastigote stage of the parasite and that the 450-nt conserved element in their 3'-UTRs is responsible for stage-specific gene regulation. We propose that the 450-nt conserved element, which is unlike any other regulatory element identified thus far, is part of a common mechanism of stage-regulated gene expression in Leishmania that regulates mRNA translation in response to intracellular stresses.