Departamento de Entomologia e Acarologia, Escola Superior de Agricultura Luiz de Queiroz - Universidade de São Paulo (USP), 13418-900, Piracicaba/SP, Brazil.
Institute for Complex Systems and Mathematical Biology, University of Aberdeen, Aberdeen, AB24 3UE, UK.
Sci Rep. 2017 Dec 12;7(1):17409. doi: 10.1038/s41598-017-17618-1.
Protein synthesis rates are determined, at the translational level, by properties of the transcript's sequence. The efficiency of an mRNA can be tuned by varying the ribosome binding sites controlling the recruitment of the ribosomes, or the codon usage establishing the speed of protein elongation. In this work we propose transcript length as a further key determinant of translation efficiency. Based on a physical model that considers the kinetics of ribosomes advancing on the mRNA and diffusing in its surrounding, as well as mRNA circularisation and ribosome drop-off, we explain how the transcript length may play a central role in establishing ribosome recruitment and the overall translation rate of an mRNA. According to our results, the proximity of the 3' end to the ribosomal recruitment site of the mRNA could induce a feedback in the translation process that would favour the recycling of ribosomes. We also demonstrate how this process may be involved in shaping the experimental ribosome density-gene length dependence. Finally, we argue that cells could exploit this mechanism to adjust and balance the usage of its ribosomal resources.
蛋白质合成速率在翻译水平上由转录本序列的特性决定。mRNA 的效率可以通过改变核糖体结合位点来调节，核糖体结合位点控制核糖体的募集，或者通过密码子使用来建立蛋白质延伸的速度。在这项工作中，我们提出转录本长度是翻译效率的另一个关键决定因素。基于一个物理模型，该模型考虑了核糖体在 mRNA 上前进和在其周围扩散的动力学，以及 mRNA 的环化和核糖体脱落，我们解释了转录本长度如何在建立核糖体募集和 mRNA 的整体翻译速率方面发挥核心作用。根据我们的结果，3' 端与 mRNA 的核糖体募集位点的接近可能会在翻译过程中引起反馈，从而有利于核糖体的回收。我们还证明了这个过程如何参与塑造实验核糖体密度-基因长度依赖性。最后，我们认为细胞可以利用这种机制来调整和平衡其核糖体资源的使用。
