Li Xia, Yagi Mieko, Morita Teppei, Aiba Hiroji
Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa, Nagoya 464-8602, Japan.
Mol Microbiol. 2008 Apr;68(2):462-73. doi: 10.1111/j.1365-2958.2008.06167.x. Epub 2008 Feb 19.
We have shown previously that ribosome stalling during translation caused by various reasons leads to mRNA cleavage, resulting in non-stop mRNAs that are eliminated in a tmRNA-dependent manner. Amino acid starvation is a physiological condition in which ribosome stalling is expected to occur more frequently. Here we demonstrate that mRNA cleavage is induced by amino acid starvation, resulting in accumulation of truncated mRNAs in cells lacking tmRNA. The truncated mRNAs are eliminated in wild-type cells, indicating that the tmRNA system rapidly degrade the truncated mRNAs. The cleavage pattern of model mRNAs in which serine codons were replaced with threonine codons indicated that mRNA cleavage occurs near serine codons in response to serine starvation. Cells lacking all of the five known toxin loci were proficient in mRNA cleavage, showing that toxin-antitoxin systems are not responsible for the cleavage. A mild serine starvation caused a significant growth inhibition in cells lacking tmRNA but not in wild-type cells. The ribosome-mediated mRNA cleavage along with the tmRNA system is an important mechanism that enables cells to adapt to amino acid starvation conditions.
我们之前已经表明，由各种原因导致的翻译过程中的核糖体停滞会引发mRNA切割，产生无终止密码子的mRNA，这些mRNA会以依赖于转移信使核糖核酸（tmRNA）的方式被清除。氨基酸饥饿是一种生理状态，预计在此状态下核糖体停滞会更频繁地发生。在此我们证明，氨基酸饥饿会诱导mRNA切割，导致在缺乏tmRNA的细胞中截短的mRNA积累。截短的mRNA在野生型细胞中被清除，这表明tmRNA系统能快速降解截短的mRNA。将丝氨酸密码子替换为苏氨酸密码子的模型mRNA的切割模式表明，响应丝氨酸饥饿时，mRNA切割发生在丝氨酸密码子附近。缺乏所有五个已知毒素位点的细胞能够进行mRNA切割，这表明毒素-抗毒素系统与切割无关。轻度丝氨酸饥饿在缺乏tmRNA的细胞中会导致显著的生长抑制，但在野生型细胞中则不会。核糖体介导的mRNA切割以及tmRNA系统是一种重要机制，使细胞能够适应氨基酸饥饿条件。
