The cell and stress‐specific canonical and noncanonical tRNA cleavage
The cell and stress‐specific canonical and noncanonical tRNA cleavage
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DOI：
10.1002/jcp.30107
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发表时间：
2020-10
影响因子：
5.6
通讯作者：
Sherif Rashad;T. Tominaga;Kuniyasu Niizuma
中科院分区：
文献类型：
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作者：
Sherif Rashad;T. Tominaga;Kuniyasu Niizuma
在应激后，转移RNA（tRNA）被切割以产生tRNA半体（tiRNA）。这些tiRNAs已经显示出抑制蛋白质翻译。血管生成素被认为是在其反密码子处切割tRNA以产生35-45个核苷酸长的tiRNA半体的主要酶，然而，最近的报告表明存在不依赖于血管生成素的切割。我们以前观察到tRNA切割模式发生远离反密码子位点。为了探索这种非典型的分裂，我们分析了tRNA的切割模式在大鼠模型的缺血再灌注和两个大鼠细胞系。在体内线粒体tRNA倾向于这种非典型的切割模式。然而，在体外，胞质和线粒体的tRNA可以被切割noncanonically。我们的研究结果显示了线粒体应激在血管生成素介导的tRNA切割中的重要调节作用。血管生成素和RNH 1似乎都不调节非经典tRNA切割。最后，我们验证了我们以前的研究结果Alkbh 1在调节tRNA切割的作用和它对非经典tRNA切割的影响。
Following stress, transfer RNA (tRNA) is cleaved to generate tRNA halves (tiRNAs). These tiRNAs have been shown to repress protein translation. Angiogenin was considered the main enzyme that cleaves tRNA at its anticodon to generate 35–45 nucleotide long tiRNA halves, however, the recent reports indicate the presence of angiogenin‐independent cleavage. We previously observed tRNA cleavage pattern occurring away from the anticodon site. To explore this noncanonical cleavage, we analyze tRNA cleavage patterns in rat model of ischemia–reperfusion and in two rat cell lines. In vivo mitochondrial tRNAs were prone to this noncanonical cleavage pattern. In vitro, however, cytosolic and mitochondrial tRNAs could be cleaved noncanonically. Our results show an important regulatory role of mitochondrial stress in angiogenin‐mediated tRNA cleavage. Neither angiogenin nor RNH1 appear to regulate the noncanonical tRNA cleavage. Finally, we verified our previous findings of the role of Alkbh1 in regulating tRNA cleavage and its impact on noncanonical tRNA cleavage.