Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are among the most ancient small RNAs in all domains of life and are generated by the cleavage of tRNAs. Emerging studies have begun to reveal the versatile roles of tsRNAs in fundamental biological processes, including gene silencing, ribosome biogenesis, retrotransposition, and epigenetic inheritance, which are rooted in tsRNA sequence conservation, RNA modifications, and protein-binding abilities. We summarize the mechanisms of tsRNA biogenesis and the impact of RNA modifications, and propose how thinking of tsRNA functionality from an evolutionary perspective urges the expansion of tsRNA research into a wider spectrum, including cross-tissue/cross-species regulation and harnessing of the 'tsRNA code' for precision medicine.

转移 RNA (tRNA) 衍生的小 RNA (tsRNA) 是生命所有领域中最古老的小 RNA 之一，由 tRNA 裂解产生。新兴研究已经开始揭示 tsRNA 在基本生物过程中的多功能作用，包括基因沉默、核糖体生物发生、逆转录转座和表观遗传，这些作用植根于 tsRNA 序列保守、RNA 修饰和蛋白质结合能力。我们总结了 tsRNA 生物发生的机制和 RNA 修饰的影响，并提出从进化角度思考 tsRNA 功能如何促使 tsRNA 研究扩展到更广泛的范围，包括跨组织/跨物种调控和利用“精准医学的 tsRNA 代码。