基因长度作为核糖体募集和蛋白质合成的调节因子：理论见解
Gene length as a regulator for ribosome recruitment and protein synthesis: theoretical insights
摘要：
蛋白质合成速率在翻译水平上由转录物序列的性质决定。mRNA的效率可以通过改变控制核糖体募集的核糖体结合位点或建立蛋白质延伸速度的密码子使用来调节。在这项工作中，我们提出转录长度作为翻译效率的进一步关键决定因素。基于一个物理模型，考虑了动力学的核糖体推进的mRNA和扩散在其周围，以及mRNA环化和核糖体脱落，我们解释了如何转录长度可能发挥核心作用，建立核糖体招聘和mRNA的整体翻译速率。根据我们的研究结果，3'端与mRNA的核糖体募集位点的接近可以在翻译过程中诱导有利于核糖体再循环的反馈。我们还展示了如何这一过程可能参与塑造实验核糖体密度基因长度依赖。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。
英文摘要：
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.
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