tRF-Gln-CTG-026 ameliorates liver injury by alleviating global protein synthesis

Sunyang Ying ^{#  1   2   3} , Pengcheng Li ^{#  1   4} , Jiaqiang Wang ^{#  1   2} , Kaiqiong Chen ^{#  1   2   3} , Yu Zou  ^{1   2   3} , Moyu Dai  ^{1   2   3} , Kai Xu  ^{1   2   5} , Guihai Feng  ^{1   2   5} , Changjian Zhang  ⁶ , Haiping Jiang  ^{1   2   3} , Wei Li  ^{1   2   3   5} , Ying Zhang  ^{7   8   9} , Qi Zhou  ^{10   11   12   13}

Affiliations

Affiliations

• ¹ State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
• ² Institute for Stem Cell and Regenerative Medicine, Chinese Academy of Sciences, Beijing, 100101, China.
• ³ University of Chinese Academy of Sciences, Beijing, 100049, China.
• ⁴ College of Life Science, Northeast Agricultural University of China, Harbin, 150030, China.
• ⁵ Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China.
• ⁶ Central Laboratory of the Sixth Medical Center of PLA General Hospital, Beijing, 100048, China.
• ⁷ State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. yingzhang@ioz.ac.cn.
• ⁸ Institute for Stem Cell and Regenerative Medicine, Chinese Academy of Sciences, Beijing, 100101, China. yingzhang@ioz.ac.cn.
• ⁹ Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China. yingzhang@ioz.ac.cn.
• ¹⁰ State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. zhouqi@ioz.ac.cn.
• ¹¹ Institute for Stem Cell and Regenerative Medicine, Chinese Academy of Sciences, Beijing, 100101, China. zhouqi@ioz.ac.cn.
• ¹² University of Chinese Academy of Sciences, Beijing, 100049, China. zhouqi@ioz.ac.cn.
• ¹³ Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China. zhouqi@ioz.ac.cn.

^# Contributed equally.

• PMID: 37015921
• PMCID: PMC10073094
• DOI: 10.1038/s41392-023-01351-5

Free PMC article

Abstract

tsRNAs (tRNA-derived small RNAs), as products of the stress response, exert considerable influence on stress response and injury regulation. However, it remains largely unclear whether tsRNAs can ameliorate liver injury. Here, we demonstrate the roles of tsRNAs in alleviating liver injury by utilizing the loss of NSun2 (NOP2/Sun domain family, member 2) as a tsRNAs-generating model. Mechanistically, the loss of NSun2 reduces methyluridine-U5 (m⁵U) and cytosine-C5 (m⁵C) of tRNAs, followed by the production of various tsRNAs, especially Class I tsRNAs (tRF-1s). Through further screening, we show that tRF-Gln-CTG-026 (tG026), the optimal tRF-1, ameliorates liver injury by repressing global protein synthesis through the weakened association between TSR1 (pre-rRNA-processing protein TSR1 homolog) and pre-40S ribosome. This study indicates the potential of tsRNA-reduced global protein synthesis in liver injury and repair, suggesting a potential therapeutic strategy for liver injury.