德国马克斯·普朗克生物化学研究所Danny D. Nedialkova团队近期取得重要工作进展，他们研究提出选择性基因表达可在分化过程中维持人类tRNA反密码子库。相关研究成果2024年1月8日在线发表于《自然—细胞生物学》杂志上。

据介绍，转运核糖核酸（tRNA）是将遗传信息转化为蛋白质所必需的。人类基因组包含数百个预测的tRNA基因，其中许多是多个拷贝。它们的表达是如何被调节以控制tRNA库的尚不清楚。

研究人员将定量tRNA图谱和染色质免疫沉淀与测序相结合，以测量人类诱导的多能干细胞分化为神经元和心脏细胞后tRNA的表达。研究人员发现tRNA转录水平差异很大，而控制解码率的tRNA反密码子库在不同细胞类型之间更稳定。从机制上讲，RNA聚合酶III在人类诱导的多能干细胞中转录广泛的tRNA基因，但在分化时被限制在定义为持家tRNA的一个子集。这种转变是由mTORC1信号传导减少介导的，mTORC1激活RNA聚合酶III阻遏物MAF1。

总之，这一研究解释了tRNA反密码子池是如何缓冲的，以保持不同细胞类型的解码速度，并揭示mTORC1在分化过程中能够驱动选择性tRNA的表达。

附：英文原文

Title: Selective gene expression maintains human tRNA anticodon pools during differentiation

Author: Gao, Lexi, Behrens, Andrew, Rodschinka, Geraldine, Forcelloni, Sergio, Wani, Sascha, Strasser, Katrin, Nedialkova, Danny D.

Issue&Volume: 2024-01-08

Abstract: Transfer RNAs are essential for translating genetic information into proteins. The human genome contains hundreds of predicted tRNA genes, many in multiple copies. How their expression is regulated to control tRNA repertoires is unknown. Here we combined quantitative tRNA profiling and chromatin immunoprecipitation with sequencing to measure tRNA expression following the differentiation of human induced pluripotent stem cells into neuronal and cardiac cells. We find that tRNA transcript levels vary substantially, whereas tRNA anticodon pools, which govern decoding rates, are more stable among cell types. Mechanistically, RNA polymerase III transcribes a wide range of tRNA genes in human induced pluripotent stem cells but on differentiation becomes constrained to a subset we define as housekeeping tRNAs. This shift is mediated by decreased mTORC1 signalling, which activates the RNA polymerase III repressor MAF1. Our data explain how tRNA anticodon pools are buffered to maintain decoding speed across cell types and reveal that mTORC1 drives selective tRNA expression during differentiation. Using modification-induced misincorporation tRNA sequencing, Gao and Behrens find that on differentiation, reduced mTORC1 signalling activates MAF1, which restricts RNA polymerase III to human tRNA housekeeping genes, to ensure that tRNA anticodon pools remain stable.

DOI: 10.1038/s41556-023-01317-3

Source: https://www.nature.com/articles/s41556-023-01317-3