芝加哥大学潘滔团队的一项最新研究显示，两种微生物代谢物竞争tRNA修饰，影响哺乳动物细胞增殖和翻译质量控制。该项研究成果发表在2025年9月16日出版的《自然—细胞生物学》上。

在这里，研究小组发现preQ₁强烈地抑制人类和母主题细胞的细胞增殖。Queuine通过与preQ₁竞争来修改相同的tRNA，从而逆转了这种效应。在小鼠的血浆和组织中可以检测到PreQ₁，在单主题癌症模型中注射它可以抑制肿瘤的生长。在机制上，preQ₁特异性地降低同源tRNA水平，以及密码子依赖性的保温基因翻译。研究人员发现内质网定位的肌醇需要酶1（IRE1）核糖核酸酶是负责翻译核糖体上preQ₁修饰的tRNA选择性降解的酶。他们的研究结果确定了两种微生物代谢物竞争宿主tRNA修饰，从而引发翻译质量控制并影响细胞增殖。

据了解，微生物组通过许多代谢物影响真核宿主细胞，包括作为宿主tRNA队列修饰底物的队列。微生物代谢产物pre-queuosine 1（preQ₁）是在细菌tRNA queue osine生物合成途径中产生的，对宿主细胞生物学的影响尚不清楚。

附：英文原文

Title: Two microbiome metabolites compete for tRNA modification to impact mammalian cell proliferation and translation quality control

Author: Zhang, Wen, Lahry, Kuldeep, Cipurko, Denis, Huang, Sihao, Zbihley, Olivia, Sevilleja, Amanda M., Rudzka, Dominika, Frietze, Luke R., Assari, Mahdi, Katanski, Christopher D., Singh, Marisha, Attina, Aurore, Guillorit, Hlne, Watkins, Christopher P., Gourlain, Delphine, Varlet, Didier, Falconi, Jennifer, Djiane, Alexandre, Hirtz, Christophe, Chen, Hankui, Macari, Franoise, Johnson, Katherine, Chevrier, Nicolas, David, Alexandre, Pan, Tao

Issue&Volume: 2025-09-16

Abstract: The microbiome affects eukaryotic host cells via many metabolites, including the well-studied queuine as substrate for host tRNA queuosine modification. The microbial metabolite pre-queuosine 1 (preQ1) is produced in the bacterial tRNA queuosine biosynthesis pathway, with unknown effects on host cell biology. Here we show that preQ1 strongly represses cell proliferation in both human and mouse cells. Queuine reverses this effect by competing with preQ1 to modify the same tRNA. PreQ1 is detectable in the plasma and tissues of mice, and its injection suppresses tumour growth in a mouse cancer model. Mechanistically, preQ1 reduces cognate tRNA levels specifically, as well as codon-dependent translation of housekeeping genes. We identify the endoplasmic reticulum-localized inositol-requiring enzyme 1 (IRE1) ribonuclease as the enzyme responsible for the selective degradation of preQ1-modified tRNAs on translating ribosomes. Our results identify two microbial metabolites competing for host tRNA modification, which elicits translation quality control and impacts cell proliferation.

DOI: 10.1038/s41556-025-01750-6

Source: https://www.nature.com/articles/s41556-025-01750-6