Length-dependent translation initiation benefits the functional proteome of human cells
Length-dependent translation initiation benefits the functional proteome of human cells
复制标题
长度依赖性翻译起始有利于人类细胞的功能蛋白质组。
DOI：
10.1039/c4mb00462k
复制
发表时间：
2015-01-01
影响因子：
--
通讯作者：
Zhang, Gong
中科院分区：
文献类型：
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作者：
Guo, Jieming;Lian, Xinlei;Zhang, Gong
我们先前发现，较短的mRNAs最好在各种真核细胞中被翻译。然而，这一现象的理论基础尚不清楚。我们假设较短的mRNA长度与降低翻译错误率相关，从而减少缺陷蛋白质降解的能量消耗。在这项研究中，我们建立了一个计算模型来解释依赖于长度的翻译启动效率。我们提供了数学证据，证明这种翻译偏好，而不是蛋白质的降解，是塑造全基因组长度依赖的蛋白质丰度的主要因素。由此推论，我们模拟了较短的mRNA长度是启动环化时间的决定因素。此外，我们的模型揭示了优先翻译较短的mRNAs有利于蛋白质组功能的能效。我们提出，癌细胞倾向于通过抵消较高的翻译错误率来劫持这一进化机制。总之，我们的模型为全球依赖长度的翻译控制的性质及其生物学意义提供了见解。
We previously found that shorter mRNAs are preferably translated in various eukaryotic cells. However, the theoretical basis of this phenomenon is unclear. We hypothesize that shorter mRNA length correlates to the decreased translational error rate to reduce the energy consumption on defective protein degradation. In this study, we established a computational model to explain the length-dependent translation initiation efficiency. We provided mathematical evidence that this translational preference, rather than the protein degradation, is a major factor to shape the genome-wide length-dependent protein abundance. As deducted, we simulated that shorter mRNA length is a determinant of initiation circularization time. Furthermore, our model unveiled that preferentially translating shorter mRNAs benefits the energy efficiency on the proteome functionality. We proposed that cancer cells tend to hijack this evolutionary mechanism by counteracting the higher translational error rate. In conclusion, our model provides insights into the nature of the global length-dependent translational control and its biological significance.