Department of Biology, Stanford University, Stanford, California, USA.
Nat Struct Mol Biol. 2014 Dec;21(12):1100-5. doi: 10.1038/nsmb.2919. Epub 2014 Nov 24.
The genetic code allows most amino acids a choice of optimal and nonoptimal codons. We report that synonymous codon choice is tuned to promote interaction of nascent polypeptides with the signal recognition particle (SRP), which assists in protein translocation across membranes. Cotranslational recognition by the SRP in vivo is enhanced when mRNAs contain nonoptimal codon clusters 35-40 codons downstream of the SRP-binding site, the distance that spans the ribosomal polypeptide exit tunnel. A local translation slowdown upon ribosomal exit of SRP-binding elements in mRNAs containing these nonoptimal codon clusters is supported experimentally by ribosome profiling analyses in yeast. Modulation of local elongation rates through codon choice appears to kinetically enhance recognition by ribosome-associated factors. We propose that cotranslational regulation of nascent-chain fate may be a general constraint shaping codon usage in the genome.
遗传密码允许大多数氨基酸有最优和非最优密码子可供选择。我们报告称，同义密码子的选择被调整为促进新生多肽与信号识别颗粒（SRP）的相互作用，SRP 有助于蛋白质跨膜转运。当 mRNA 中含有非最优密码子簇（距离核糖体多肽出口隧道跨越 35-40 个密码子）位于 SRP 结合位点下游时，SRP 在体内的共翻译识别会增强。酵母核糖体图谱分析实验支持了在含有这些非最优密码子簇的 mRNA 中，当核糖体出口的 SRP 结合元件时，核糖体出口处的局部翻译减速。通过密码子选择调节局部延伸率似乎在动力学上增强了核糖体相关因子的识别。我们提出，新生链命运的共翻译调控可能是塑造基因组中密码子使用的一般约束。
