Chavancy G, Garel J P
Biochimie. 1981 Mar;63(3):187-95. doi: 10.1016/s0300-9084(81)80192-7.
Neither a dynamic nor an energetic approach of the translation process has taken into account that intracellular levels of iso-tRNA species are adapted or adjusted to the codon frequency of mRNA being decoded (Bombyx mori silk gland, rabbit reticulocyte). A critical study of available experimental data suggests that the average elongation rate of a protein is maximized in the presence of an adapted tRNA population, usually an homologous tRNA. In addition, the amount of synthesized protein parallels that of corresponding mRNA. Other evidences--including in vitro and in vivo elongation assays with fibroin mRNA--show that individual elongation rates are not uniform. Pauses occur at certain sites of the mRNA chain. The relative lifetime of these pauses depends on the tRNA pool used. Finally, it appears that translation accuracy also depends on the balanced tRNA population. We propose to explain these different effects by using a codon-anticodon recognition model, called "trial and error system" based on a stochastic processing of the ribosome. Accordingly, various acylated tRNA species which surround a ribosome randomly encounter the receptor A site. Every trapped tRNA species is tested for a proper pairing with the codon to be recognized at the level of a comparator or discriminator function. If the pairing is correct, transpeptidation becomes irreversible. If not, the aminoacyl-tRNA is rejected and another randomly trapped tRNA is processed in turn. Mathematical analysis of this model shows that the mean number of trials used for translating the whole sequence of a mRNA is minimized when the proportion of different iso-tRNA species is correlated with the square root of codon frequency. Quantitations of reticulocyte tRNA support such a parabolic relation. Our translation system model brings some light into the role of tRNA adaptation for optimizing translation efficiency, i.e. maximizing both speed and accuracy. Some consequences of the model are discussed.
无论是翻译过程的动态方法还是能量方法，都没有考虑到细胞内同工tRNA种类的水平会根据正在解码的mRNA的密码子频率进行调整（家蚕丝腺、兔网织红细胞）。对现有实验数据的批判性研究表明，在存在适配的tRNA群体（通常是同源tRNA）的情况下，蛋白质的平均延伸速率会最大化。此外，合成蛋白质的量与相应mRNA的量平行。其他证据——包括用丝心蛋白mRNA进行的体外和体内延伸试验——表明个体延伸速率并不均匀。在mRNA链的某些位点会出现停顿。这些停顿的相对持续时间取决于所使用的tRNA库。最后，翻译准确性似乎也取决于平衡的tRNA群体。我们建议通过使用一种密码子 - 反密码子识别模型来解释这些不同的效应，该模型基于核糖体的随机处理，称为“试错系统”。因此，围绕核糖体的各种酰化tRNA种类随机遇到受体A位点。每个捕获的tRNA种类都要在比较器或鉴别功能水平上测试与要识别的密码子的正确配对。如果配对正确，转肽反应就会变得不可逆。如果不正确，氨酰 - tRNA就会被拒绝，然后依次处理另一个随机捕获的tRNA。对该模型的数学分析表明，当不同同工tRNA种类的比例与密码子频率的平方根相关时，用于翻译mRNA整个序列的平均试验次数会最小化。对网织红细胞tRNA的定量支持这种抛物线关系。我们的翻译系统模型揭示了tRNA适配在优化翻译效率（即最大化速度和准确性）方面的作用。讨论了该模型的一些后果。
