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Mammalian tRNA acetylation determines translation efficiency and tRNA quality control

Author

Listed:
  • Na Liu

    (University of Chinese Academy of Sciences
    Shanghai Jiao Tong University)

  • Bingxue Liu

    (Hunan University)

  • Chun-Rui Ma

    (University of Chinese Academy of Sciences)

  • Zixin Cai

    (Hunan University)

  • Jin-Tao Wang

    (University of Chinese Academy of Sciences)

  • Zi-Qing Chai

    (University of Chinese Academy of Sciences)

  • Nanlin Zhu

    (Chinese Academy of Sciences)

  • Ting Shao

    (Chinese Academy of Sciences)

  • Yue-Lei Chen

    (Chinese Academy of Sciences)

  • Yu Lin

    (Shanghai Jiao Tong University)

  • Yirong Wang

    (Hunan University)

  • Hong Xu

    (Shanghai Jiao Tong University)

  • Xiao-Long Zhou

    (University of Chinese Academy of Sciences)

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.

Suggested Citation

  • 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, 2025. "Mammalian tRNA acetylation determines translation efficiency and tRNA quality control," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60723-3
    DOI: 10.1038/s41467-025-60723-3
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    References listed on IDEAS

    as
    1. Song Xiang & Amalene Cooper-Morgan & Xinfu Jiao & Megerditch Kiledjian & James L. Manley & Liang Tong, 2009. "Structure and function of the 5′→3′ exoribonuclease Rat1 and its activating partner Rai1," Nature, Nature, vol. 458(7239), pages 784-788, April.
    2. Aldema Sas-Chen & Justin M. Thomas & Donna Matzov & Masato Taoka & Kellie D. Nance & Ronit Nir & Keri M. Bryson & Ran Shachar & Geraldy L. S. Liman & Brett W. Burkhart & Supuni Thalalla Gamage & Yuko , 2020. "Dynamic RNA acetylation revealed by quantitative cross-evolutionary mapping," Nature, Nature, vol. 583(7817), pages 638-643, July.
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