Laboratory of Bioinformatics, Institute of Microbiology, Academy of Sciences of Czech Republic, v.v.i., 14220 Prague, Videnska 1083, Czech Republic, Laboratory of Genomics and Bioinformatics, Institute of Molecular Genetics, Academy of Sciences of Czech Republic, v.v.i., 14220 Prague, Videnska 1083, Czech Republic and Laboratory of Regulation of Gene Expression, Institute of Microbiology, Academy of Sciences of Czech Republic, v.v.i., 14220 Prague, Videnska 1083, Czech Republic.
Nucleic Acids Res. 2013 Sep;41(16):7625-34. doi: 10.1093/nar/gkt548. Epub 2013 Jun 26.
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.
有几种关键的机制可以在蛋白质合成水平上调节真核基因表达。有趣的是,翻译控制中探索最少的机制是那些涉及翻译核糖体本身的机制,例如通过预测核糖体 RNA(rRNA)和 mRNA 之间的相互作用来介导。在这里,我们利用大量生物体的 mRNA 序列的稳健增长的大规模数据集、核糖体结构和计算能力,通过计算来探索在物种间具有统计学意义的 mRNA-rRNA 互补性。我们的预测揭示了 18S rRNA 序列与 mRNA5'非翻译区(UTR)之间的高度特异性序列互补性,在 40S 亚基的 rRNA 序列上形成了一个明确的三维模式。这种模式更广泛的进化保守性可能意味着,已经从 mRNA 结合通道中出现的真核 mRNA 的 5'UTR 可能与位于 mRNA 结合通道出口附近以及溶剂暴露的 40S 核糖体的中下部(包括其左脚)的几个互补点的 18S rRNA 接触。我们讨论了这种结构保守模式的生理意义,并结合以前发表的实验结果,提出它调节了通过 mRNA 的 40S 亚基的扫描。