Translation In Amino-Acid-Poor Environments Is Limited By Trna(Gl)(N) Charging
ELIFE(2020)
摘要
An inadequate supply of amino acids leads to accumulation of uncharged tRNAs, which can bind and activate GCN2 kinase to reduce translation. Here, we show that glutamine-specific tRNAs selectively become uncharged when extracellular amino acid availability is compromised. In contrast, all other tRNAs retain charging of their cognate amino acids in a manner that is dependent upon intact lysosomal function. In addition to GCN2 activation and reduced total translation, the reduced charging of tRNA(Gl)(n) in amino-acid-deprived cells also leads to specific depletion of proteins containing polyglutamine tracts including core-binding factor al, mediator subunit 12, transcriptional coactivator CBP and TATA-box binding protein. Treating amino-aciddeprived cells with exogenous glutamine or glutaminase inhibitors restores tRNA(Gl)(n) charging and the levels of polyglutamine-containing proteins. Together, these results demonstrate that the activation of GCN2 and the translation of polyglutamine-encoding transcripts serve as key sensors of glutamine availability in mammalian cells.
更多查看译文
关键词
cell biology,human,mouse
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要