Ribosome profiling reveals sequence-independent post-initiation pausing as a signature of translation
Ribosome profiling reveals sequence-independent post-initiation pausing as a signature of translation
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DOI：
10.1038/cr.2014.74
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发表时间：
2014-07-01
期刊：
影响因子：
44.1
通讯作者：
Qian, Shu-Bing
中科院分区：
文献类型：
--
作者：
Han, Yan;Gao, Xiangwei;Qian, Shu-Bing
新合成的多肽的旅程始于核糖体的肽基转移酶中心，从那里穿过出口隧道。核糖体出口通道的内部既不直也不光滑。体内核糖体动力学如何受到出口通道的影响还知之甚少。哺乳动物细胞中的全基因组核糖体分析揭示了在起始密码子处核糖体密度升高，并且令人惊讶地在下游第5密码子位置处也是如此。我们发现，高度集中的核糖体暂停后不久开始归因于出口隧道的几何形状，从核糖体蛋白L4的环区的删除减少翻译暂停在第5密码子的位置。出乎意料的是，核糖体变体在起始后不久就经历了翻译放弃，这表明在起始和延伸承诺之间存在强制性步骤。我们建议，后启动暂停的核糖体的翻译机器，以确保生产性翻译的固有签名。
The journey of a newly synthesized polypeptide starts in the peptidyltransferase center of the ribosome, from where it traverses the exit tunnel. The interior of the ribosome exit tunnel is neither straight nor smooth. How the ribosome dynamics in vivo is influenced by the exit tunnel is poorly understood. Genome-wide ribosome profiling in mammalian cells reveals elevated ribosome density at the start codon and surprisingly the downstream 5th codon position as well. We found that the highly focused ribosomal pausing shortly after initiation is attributed to the geometry of the exit tunnel, as deletion of the loop region from ribosome protein L4 diminishes translational pausing at the 5th codon position. Unexpectedly, the ribosome variant undergoes translational abandonment shortly after initiation, suggesting that there exists an obligatory step between initiation and elongation commitment. We propose that the post-initiation pausing of ribosomes represents an inherent signature of the translation machinery to ensure productive translation.