Hockenberry Adam J, Pah Adam R, Jewett Michael C, Amaral Luís A N
Interdisciplinary Program in Biological Sciences, Northwestern University, Evanston, IL 60208, USA.
Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, USA.
Open Biol. 2017 Jan;7(1). doi: 10.1098/rsob.160239.
Studies dating back to the 1970s established that sequence complementarity between the anti-Shine-Dalgarno (aSD) sequence on prokaryotic ribosomes and the 5' untranslated region of mRNAs helps to facilitate translation initiation. The optimal location of aSD sequence binding relative to the start codon, the full extents of the aSD sequence and the functional form of the relationship between aSD sequence complementarity and translation efficiency have not been fully resolved. Here, we investigate these relationships by leveraging the sequence diversity of endogenous genes and recently available genome-wide estimates of translation efficiency. We show that-after accounting for predicted mRNA structure-aSD sequence complementarity increases the translation of endogenous mRNAs by roughly 50%. Further, we observe that this relationship is nonlinear, with translation efficiency maximized for mRNAs with intermediate levels of aSD sequence complementarity. The mechanistic insights that we observe are highly robust: we find nearly identical results in multiple datasets spanning three distantly related bacteria. Further, we verify our main conclusions by re-analysing a controlled experimental dataset.
追溯到20世纪70年代的研究表明，原核生物核糖体上的抗Shine-Dalgarno（aSD）序列与mRNA的5'非翻译区之间的序列互补性有助于促进翻译起始。aSD序列结合相对于起始密码子的最佳位置、aSD序列的完整范围以及aSD序列互补性与翻译效率之间关系的功能形式尚未完全解决。在这里，我们通过利用内源基因的序列多样性和最近可用的全基因组翻译效率估计来研究这些关系。我们表明，在考虑预测的mRNA结构后，aSD序列互补性使内源mRNA的翻译增加了约50%。此外，我们观察到这种关系是非线性的，对于具有中等水平aSD序列互补性的mRNA，翻译效率最高。我们观察到的机制见解非常稳健：我们在跨越三种远缘相关细菌的多个数据集中发现了几乎相同的结果。此外，我们通过重新分析一个受控实验数据集验证了我们的主要结论。
