tRNAs are key adaptor molecules that decipher the genetic code during translation of mRNAs in protein synthesis. In contrast to the traditional view of tRNAs as ubiquitously expressed housekeeping molecules, awareness is now growing that tRNA-encoding genes display tissue-specific and cell type-specific patterns of expression, and that tRNA gene expression and function are both dynamically regulated by post-transcriptional RNA modifications. Moreover, dysregulation of tRNAs, mediated by alterations in either their abundance or function, can have deleterious consequences that contribute to several distinct human diseases, including neurological disorders and cancer. Accumulating evidence shows that reprogramming of mRNA translation through altered tRNA activity can drive pathological processes in a codon-dependent manner. This Review considers the emerging evidence in support of the precise control of functional tRNA levels as an important regulatory mechanism that coordinates mRNA translation and protein expression in physiological cell homeostasis, and highlights key examples of human diseases that are linked directly to tRNA dysregulation.

tRNA 是蛋白质合成中 mRNA 翻译过程中破译遗传密码的关键接头分子。与 tRNA 作为普遍表达的管家分子的传统观点相反，现在人们越来越认识到 tRNA 编码基因表现出组织特异性和细胞类型特异性的表达模式，并且 tRNA 基因表达和功能均受到后处理的动态调节。转录RNA修饰。此外，由丰度或功能改变介导的 tRNA 失调可能会产生有害后果，导致多种不同的人类疾病，包括神经系统疾病和癌症。越来越多的证据表明，通过改变 tRNA 活性对 mRNA 翻译进行重编程可以以密码子依赖性方式驱动病理过程。本综述考虑了支持精确控制功能性 tRNA 水平作为协调生理细胞稳态中 mRNA 翻译和蛋白质表达的重要调节机制的新证据，并强调了与 tRNA 失调直接相关的人类疾病的关键例子。