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.He...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(m^(5)U)and cytosine-C5(m^(5)C)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.展开更多
基金supported by grants from the National Key Research and Development Program (2019YFA0110900 to G.F.,2018YFA0108500,2019YFA0110800 to W.L.)the National Natural Science Foundation of China (31621004 to Q.Z.and W.L.,81972633 to Y.Z.)+1 种基金CAS Project for Young Scientists in Basic Research (YSBR-012 to W.L.)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16030400 to W.L.).
文摘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(m^(5)U)and cytosine-C5(m^(5)C)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.
