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An evolutionary conserved pattern of 18S rRNA sequence complementarity to mRNA 5′ UTRs and its implications for eukaryotic gene translation regulation

机译:18S rRNA序列与mRNA 5UTR互补的进化保守模式及其对真核基因翻译调控的意义

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摘要

There are several key mechanisms regulating eukaryotic gene expression at the level of protein synthesis. Interestingly, the least explored mechanisms of translational control are those that involve the translating ribosome per se, mediated for example via predicted interactions between the ribosomal RNAs (rRNAs) and mRNAs. Here, we took advantage of robustly growing large-scale data sets of mRNA sequences for numerous organisms, solved ribosomal structures and computational power to computationally explore the mRNA–rRNA complementarity that is statistically significant across the species. Our predictions reveal highly specific sequence complementarity of 18S rRNA sequences with mRNA 5′ untranslated regions (UTRs) forming a well-defined 3D pattern on the rRNA sequence of the 40S subunit. Broader evolutionary conservation of this pattern may imply that 5′ UTRs of eukaryotic mRNAs, which have already emerged from the mRNA-binding channel, may contact several complementary spots on 18S rRNA situated near the exit of the mRNA binding channel and on the middle-to-lower body of the solvent-exposed 40S ribosome including its left foot. We discuss physiological significance of this structurally conserved pattern and, in the context of previously published experimental results, propose that it modulates scanning of the 40S subunit through 5′ UTRs of mRNAs.
机译:在蛋白质合成水平上,有几种调节真核基因表达的关键机制。有趣的是,最少研究的翻译控制机制是那些涉及翻译核糖体本身的机制,例如通过核糖体RNA(rRNA)和mRNA之间的预测相互作用介导的。在这里,我们利用了为各种生物体快速增长的大规模mRNA序列数据集,解决的核糖体结构和计算能力来计算探索整个物种具有统计学意义的mRNA-rRNA互补性。我们的预测揭示了18S rRNA序列与mRNA 5'非翻译区(UTR)在40S亚基的rRNA序列上形成明确定义的3D模式的高度特异性的序列互补性。该模式的更广泛的进化保守性可能暗示已经从mRNA结合通道中出现的真核mRNA的5'UTR可能与18S rRNA上位于mRNA结合通道出口附近和中间至-溶剂暴露的40S核糖体的下半身,包括其左脚。我们讨论这种结构保守模式的生理意义,并在以前发表的实验结果的上下文中,提出它通过mRNA的5'UTR调节40S亚基的扫描。

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