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首页> 外文期刊>Parasitology >Messenger RNAs with large numbers of upstream open reading frames are translated via leaky scanning and reinitiation in the asexual stages of Plasmodium falciparum
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Messenger RNAs with large numbers of upstream open reading frames are translated via leaky scanning and reinitiation in the asexual stages of Plasmodium falciparum

机译：具有大量上游开放阅读框架的Messenger RNA通过泄漏扫描和重新加固了疟原虫的疟原虫阶段

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摘要

The genome of Plasmodium falciparum has one of the most skewed base-pair compositions of any eukaryote, with an AT content of 80-90%. As start and stop codons are AT-rich, the probability of finding upstream open reading frames (uORFs) in messenger RNAs (mRNAs) is high and parasite mRNAs have an average of 11 uORFs in their leader sequences. Similar to other eukaryotes, uORFs repress the translation of the downstream open reading frame (dORF) in P. falciparum, yet the parasite translation machinery is able to bypass these uORFs and reach the dORF to initiate translation. This can happen by leaky scanning and/or reinitiation.In this report, we assessed leaky scanning and reinitiation by studying the effect of uORFs on the translation of a dORF, in this case, the luciferase reporter gene, and showed that both mechanisms are employed in the asexual blood stages of P. falciparum. Furthermore, in addition to the codon usage of the uORF, translation of the dORF is governed by the Kozak sequence and length of the uORF, and inter-cistronic distance between the uORF and dORF. Based on these features whole-genome data was analysed to uncover classes of genes that might be regulated by uORFs. This study indicates that leaky scanning and reinitiation appear to be widespread in asexual stages of P. falciparum, which may require modifications of existing factors that are involved in translation initiation in addition to novel, parasite-specific proteins.
机译：恶性疟原虫基因组是所有真核生物中最扭曲的碱基对组成之一，AT含量为80-90%。由于起始密码子和终止密码子丰富，在信使RNA（mRNAs）中发现上游开放阅读框（UORF）的概率很高，寄生虫mRNAs的前导序列中平均有11个UORF。与其他真核生物类似，UORF抑制恶性疟原虫下游开放阅读框（dORF）的翻译，但寄生虫翻译机制能够绕过这些UORF，到达dORF启动翻译。这可以通过泄漏扫描和/或重新初始化来实现。在本报告中，我们通过研究uORFs对dORF（在本例中为荧光素酶报告基因）翻译的影响来评估漏检扫描和重新启动，并表明这两种机制均适用于恶性疟原虫的无性血液阶段。此外，除了uORF的密码子用法外，dORF的翻译还受Kozak序列和uORF的长度以及uORF和dORF之间的顺电子距离的控制。基于这些特征，对整个基因组数据进行了分析，以发现可能受UORF调控的基因类别。这项研究表明，漏扫描和重新启动似乎在恶性疟原虫的无性阶段很普遍，除了新的寄生虫特异性蛋白质外，可能还需要修改参与翻译启动的现有因素。

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