Accurate Recovery of Ribosome Positions Reveals Slow Translation of Wobble-Pairing Codons in Yeast.
Accurate Recovery of Ribosome Positions Reveals Slow Translation of Wobble-Pairing Codons in Yeast.
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DOI：
10.1089/cmb.2016.0147
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发表时间：
2017-06
期刊：
影响因子：
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通讯作者：
Kingsford C
中科院分区：
文献类型：
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作者：
Wang H;McManus J;Kingsford C
核糖体分析定量捕获翻译过程中的核糖体位置。所得到的核糖体位置谱被广泛用于研究翻译速度。然而，对核糖体位置的准确估计依赖于从核糖体分析读取中识别a位点，这是一个以前没有解决的问题。在这里，我们提出了一种新的方法来估计核糖体a -位点的位置从高覆盖率的核糖体分析读取。我们的模型允许使用更多的读取，准确地解释了不同长度的核糖体分析读取的3-nt周期性，并恢复了不同长度的一致核糖体位置。我们恢复的核糖体位置正确地高度倾斜于密码子内的单个帧。它们保留子密码子分辨率，并能够检测帧外翻译事件，如帧移位。我们的方法提高了与其他密码子解码时间估计的相关性。此外，改进后的图谱显示，酵母摆动配对密码子的翻译速度比其同义的沃森-克里克配对密码子慢。这些结果提供了蛋白质合成速率可以通过密码子使用偏差调节的证据。
Ribosome profiling quantitatively captures ribosome locations during translation. The resulting profiles of ribosome locations are widely used to study translational speed. However, an accurate estimation of the ribosome location depends on identifying the A-site from ribosome profiling reads, a problem that was previously unsolved. Here, we propose a novel method to estimate the ribosome A-site positions from high-coverage ribosome profiling reads. Our model allows more reads to be used, accurately explains the 3-nt periodicity of ribosome profiling reads from various lengths, and recovers consistent ribosome positions across different lengths. Our recovered ribosome positions are correctly highly skewed toward a single frame within a codon. They retain subcodon resolution and enable detection of off-frame translational events, such as frameshifts. Our method improves the correlation with other estimates of codon decoding time. Furthermore, the refined profiles show that yeast wobble-pairing codons are translated slower than their synonymous Watson–Crick-pairing codons. These results provide evidence that protein synthetic rate can be tuned by codon usage bias.