Cleavage of the A site mRNA codon during ribosome pausing provides a mechanism for translational quality control

Cleavage of the A site mRNA codon during ribosome pausing provides a mechanism for translational quality control
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DOI:
10.1016/s1097-2765(03)00385-x
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发表时间:
2003-10-01
期刊:
影响因子:
16
通讯作者:
Sauer, RT
Sauer, RT
中科院分区:
生物学1区
文献类型:
--
作者:
Hayes, CS;Sauer, RT

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细胞采用多种机制来确保蛋白质生物合成过程中的质量控制。在这里,我们发现,在细菌核糖体暂停期间,正在翻译的 mRNA 在 A 位点密码子内或紧邻 A 位点密码子的位点被切割。该 A 位点 mRNA 裂解的程度与核糖体暂停的程度相关,如通过新生多肽的 tmRNA 介导的标记所测定的。裂解不需要 tmRNA、核糖体报警素 (p)ppGpp 或细菌毒素(例如 RelE),这些毒素已被证明可以刺激类似的活性。切割需要翻译,这表明核糖体以某种方式参与反应。当正常蛋白质合成受到损害时,A 位点 mRNA 裂解和 tmRNA 系统提供了一种减少翻译错误以及异常和潜在有害多肽产生的机制。
Cells employ many mechanisms to ensure quality control during protein biosynthesis. Here, we show that, during the pausing of a bacterial ribosome, the mRNA being translated is cleaved at a site within or immediately adjacent to the A site codon. The extent of this A site mRNA cleavage is correlated with the extent of ribosome pausing as assayed by tmRNA-mediated tagging of the nascent polypeptide. Cleavage does not require tmRNA, the ribosomal alarmone (p)ppGpp, or bacterial toxins such as RelE which have been shown to stimulate a similar activity. Translation is required for cleavage, suggesting that the ribosome participates in the reaction in some fashion. When normal protein synthesis is compromised, A site mRNA cleavage and the tmRNA system provide a mechanism for reducing translational errors and the production of aberrant and potentially harmful polypeptides.