A growing class of small RNAs, known as tRNA-derived RNAs (tdRs), tRNA-derived small RNAs or tRNA-derived fragments, have long been considered mere intermediates of tRNA degradation. These small RNAs have recently been implicated in an evolutionarily conserved repertoire of biological processes. In this Review, we discuss the biogenesis and molecular functions of tdRs in mammals, including tdR-mediated gene regulation in cell metabolism, immune responses, transgenerational inheritance, development and cancer. We also discuss the accumulation of tRNA-derived stress-induced RNAs as a distinct adaptive cellular response to pathophysiological conditions. Furthermore, we highlight new conceptual advances linking RNA modifications with tdR activities and discuss challenges in studying tdR biology in health and disease.

越来越多的小 RNA，称为 tRNA 衍生的 RNA (tdR)、tRNA 衍生的小 RNA 或 tRNA 衍生的片段，长期以来一直被认为仅仅是 tRNA 降解的中间体。这些小RNA最近被认为参与了进化上保守的生物过程。在这篇综述中，我们讨论了哺乳动物中 tdR 的生物发生和分子功能，包括细胞代谢、免疫反应、跨代遗传、发育和癌症中 tdR 介导的基因调控。我们还讨论了 tRNA 衍生的应激诱导 RNA 的积累，作为对病理生理条件的独特适应性细胞反应。此外，我们重点介绍了将 RNA 修饰与 tdR 活性联系起来的新概念进展，并讨论了研究健康和疾病中 tdR 生物学的挑战。