{"title":"Mammalian tRNA acetylation determines translation efficiency and tRNA quality control.","authors":"Na Liu, Bingxue Liu, Chun-Rui Ma, Zixin Cai, Jin-Tao Wang, Zi-Qing Chai, Nanlin Zhu, Ting Shao, Yue-Lei Chen, Yu Lin, Yirong Wang, Hong Xu, Xiao-Long Zhou","doi":"10.1038/s41467-025-60723-3","DOIUrl":null,"url":null,"abstract":"<p><p>Acetylation is a conserved and pivotal RNA modification. Acetylation of tRNA occurs at C12 (ac<sup>4</sup>C12) in eukaryotic tRNAs. Yeast ac<sup>4</sup>C12 prevents tRNA<sup>Ser</sup> from rapid tRNA decay (RTD) at higher temperatures. However, the biological function of ac<sup>4</sup>C12 in higher eukaryotes remains unexplored. Moreover, whether mammalian cells contain an RTD pathway is unclear. Here, we deleted Thumpd1, the indispensable factor for ac<sup>4</sup>C12 biogenesis, in NIH/3T3 cells. Loss of ac<sup>4</sup>C12 significantly reduced tRNA aminoacylation and translational efficiency physiologically, in particular, of those enriched with Ser/Leu codons with two U/A nucleotides. Remarkably, ac<sup>4</sup>C12 hypomodification selectively generated rapid tRNA<sup>Leu</sup>(CAG) turnover under heat stress. We demonstrated that tRNA<sup>Leu</sup>(CAG) was degraded by a mammalian RTD (mRTD) mechanism, consisting of Xrn1/Xrn2-mediated 5'-3' exonuclease digestion and intracellular pAp level control by Bpnt1/Bpnt2. Our results reveal both the pivotal roles of ac<sup>4</sup>C12 in translation and a mRTD pathway for tRNA quality control under heat stress in mammalian cells.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"16 1","pages":"5496"},"PeriodicalIF":15.7000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215905/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Communications","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41467-025-60723-3","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Acetylation is a conserved and pivotal RNA modification. Acetylation of tRNA occurs at C12 (ac4C12) in eukaryotic tRNAs. Yeast ac4C12 prevents tRNASer from rapid tRNA decay (RTD) at higher temperatures. However, the biological function of ac4C12 in higher eukaryotes remains unexplored. Moreover, whether mammalian cells contain an RTD pathway is unclear. Here, we deleted Thumpd1, the indispensable factor for ac4C12 biogenesis, in NIH/3T3 cells. Loss of ac4C12 significantly reduced tRNA aminoacylation and translational efficiency physiologically, in particular, of those enriched with Ser/Leu codons with two U/A nucleotides. Remarkably, ac4C12 hypomodification selectively generated rapid tRNALeu(CAG) turnover under heat stress. We demonstrated that tRNALeu(CAG) was degraded by a mammalian RTD (mRTD) mechanism, consisting of Xrn1/Xrn2-mediated 5'-3' exonuclease digestion and intracellular pAp level control by Bpnt1/Bpnt2. Our results reveal both the pivotal roles of ac4C12 in translation and a mRTD pathway for tRNA quality control under heat stress in mammalian cells.
期刊介绍：
Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.
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