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首页> 外文期刊>Journal of Molecular Biology >The functional half-life of an mRNA depends on the ribosome spacing in an early coding region.
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The functional half-life of an mRNA depends on the ribosome spacing in an early coding region.

机译：mRNA的功能半衰期取决于早期编码区域中核糖体的间隔。

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摘要

Bacterial mRNAs are translated by closely spaced ribosomes and degraded from the 5'-end, with half-lives of around 2 min at 37 degrees C in most cases. Ribosome-free or "naked" mRNA is known to be readily degraded, but the initial event that inactivates the mRNA functionally has not been fully described. Here, we characterize a determinant of the functional stability of an mRNA, which is located in the early coding region. Using literature values for the mRNA half-lives of variant lacZ mRNAs in Escherichia coli, we modeled how the ribosome spacing is affected by the translation rate of the individual codons. When comparing the ribosome spacing at various segments of the mRNA to its functional half-life, we found a clear correlation between the functional mRNA half-life and the ribosome spacing in the mRNA region approximately between codon 20 and codon 45. From this finding, we predicted that inserts of slowly translated codons before codon 20 or after codon 45 should shorten or prolong, respectively, the functional mRNA half-life by altering the ribosome density in the important region. These predictions were tested on eight new lacZ variants, and their experimentally determined mRNA half-lives all supported the model. We thus suggest that translation-rate-mediated differences in the spacing between ribosomes in this early coding region is a parameter that determines the mRNAs functional half-life. We present a model that is in accordance with many earlier observations and that allows a prediction of the functional half-life of a given mRNA sequence.
机译：细菌mRNA由紧密排列的核糖体翻译并从5'端降解，在大多数情况下，其在37摄氏度下的半衰期约为2分钟。已知无核糖体或“裸” mRNA易于降解，但是尚未完全描述使mRNA功能失活的初始事件。在这里，我们表征了位于早期编码区域的mRNA功能稳定性的决定因素。使用变体lacZ mRNA在大肠杆菌中的mRNA半衰期的文献价值，我们对核糖体间距如何受单个密码子的翻译率影响进行了建模。当将mRNA各个部分的核糖体间距与其功能性半衰期进行比较时，我们发现功能性mRNA半衰期与mRNA区域中大约在20号密码子和45号密码子之间的核糖体间距之间存在明显的相关性。我们预测，在20号密码子之前或45号密码子之后，缓慢翻译的密码子插入片段应通过改变重要区域的核糖体密度分别缩短或延长功能性mRNA半衰期。这些预测在八个新的lacZ变体上进行了测试，并且它们通过实验确定的mRNA半衰期均支持该模型。因此，我们建议在此早期编码区中核糖体之间的间隔中翻译率介导的差异是决定mRNA功能半衰期的参数。我们提出了一种模型，该模型与许多早期观察结果一致，并且可以预测给定mRNA序列的功能半衰期。

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