Messenger RNAs with large numbers of upstream open reading frames are translated via leaky scanning and reinitiation in the asexual stages of Plasmodium falciparum
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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DOI：
10.1017/s0031182020000840
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发表时间：
2020-09-01
期刊：
影响因子：
2.4
通讯作者：
Patankar, Swati
中科院分区：
文献类型：
--
作者：
Kaur, Chhaminder;Kumar, Mayank;Patankar, Swati
恶性疟原虫的基因组是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富含AT，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的前导序列平均有11个uORF。与其他真核生物类似，uORF抑制下游开放阅读框架(DORF)INP的翻译。然而，寄生虫翻译机制能够绕过这些uORF，到达DORF来启动翻译。这可能通过泄漏扫描和/或重新启动来实现。在这份报告中，我们通过研究uORFs对DORF(在这种情况下是荧光素酶报告基因)翻译的影响来评估泄漏扫描和重新启动，并表明这两种机制都适用于无性血液阶段的OFP。恶性疟原虫。此外，除了uORF的密码子使用之外，DORF的翻译还受uORF的Kozak序列和长度以及uORF和DORF之间的顺反子距离的影响。基于这些特征，对全基因组数据进行了分析，以揭示可能受uORF调控的基因类别。这项研究表明，泄漏扫描和重新启动似乎在OFP的无性阶段普遍存在。恶性疟原虫，这可能需要修改参与翻译启动的现有因子，以及新的寄生虫特异性蛋白。
The genome ofPlasmodium falciparumhas 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) inP. 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 ofP. 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 ofP. falciparum, which may require modifications of existing factors that are involved in translation initiation in addition to novel, parasite-specific proteins.