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Updated: Sep 17, 2025
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Polysome Fractionation and Analysis of Mammalian Translatomes on a Genome-wide Scale
Published on: May 17, 2014
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Mammalian tRNA acetylation determines translation efficiency and tRNA quality control
Na Liu1,2, Bingxue Liu3, Chun-Rui Ma1
1State Key Laboratory of RNA Innovation, Science and Engineering, CAS center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Nature Communications
|July 2, 2025
Summary
Mammalian cells utilize ac4C12 RNA modification to maintain translation efficiency. Loss of this modification triggers rapid tRNA decay under heat stress, revealing a novel quality control pathway.
Area of Science:
- Molecular Biology
- RNA Biology
- Post-transcriptional Modifications
Background:
- Acetylation of tRNA at C12 (ac4C12) is a conserved RNA modification.
- Yeast ac4C12 prevents tRNA decay at high temperatures, but its role in mammals is unknown.
- The existence of a rapid tRNA decay (RTD) pathway in mammalian cells is unclear.
Purpose of the Study:
- To investigate the biological function of ac4C12 in higher eukaryotes.
- To determine if mammalian cells possess an RTD pathway.
- To elucidate the role of ac4C12 in tRNA quality control and translation under stress.
Main Methods:
- Deletion of Thumpd1, essential for ac4C12 biogenesis, in NIH/3T3 cells.
- Analysis of tRNA aminoacylation and translational efficiency.
- Investigation of tRNA turnover under heat stress.
- Characterization of the mammalian RTD (mRTD) mechanism.
Main Results:
- Loss of ac4C12 reduced tRNA aminoacylation and translational efficiency.
- ac4C12 hypomodification led to selective rapid tRNA^Leu(CAG) turnover under heat stress.
- A mammalian RTD pathway involving Xrn1/Xrn2 and Bpnt1/Bpnt2 was identified.
Conclusions:
- ac4C12 plays a crucial role in maintaining translation efficiency in mammalian cells.
- Mammalian cells have a heat-inducible RTD pathway for tRNA quality control.
- This study reveals the significance of ac4C12 and the mRTD pathway in cellular response to heat stress.
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