{"id":526,"title":"Direct regulation of a tRNA modification enzyme by ppGpp links stress signaling to translational control and biofilm development","title_zh":"ppGpp 直接调控 tRNA 修饰酶，将应激信号与翻译控制及生物膜发育联系起来","url":"https://doi.org/10.1126/sciadv.aek6976","doi":"10.1126/sciadv.aek6976","pmid":null,"journal":"Science Advances","kind":"paper","lang":"en","published_at":"2026-11-06T00:00:00+00:00","fetched_at":"2026-11-08T03:45:21+00:00","authors":["Aude E. Trinquier","Franck Slama","Junlang Liu","Lucille Pham","Lauren Stolt","Jue D. Wang"],"primary_topic":"ethics-policy","topics":[{"slug":"ethics-policy","score":4.0,"hits":["regulation"]}],"topic_score":4.0,"preference_score":0.0,"preference_labels":[],"llm_score":34.0,"final_score":42.0,"score_dims":{"novelty":80,"rigor":82,"impact":22,"relevance":8,"translation":10},"recommend_reason":"机制研究扎实、新颖（ppGpp 直接抑制 tRNA 修饰酶并重塑密码子特异性翻译），但研究对象为细菌生物膜形成，与生殖医学、辅助生殖及胚胎多组学几乎无直接关联，对本领域读者的参考价值有限。","keywords":["ppGpp","tRNA 修饰","MnmE/TrmE","核糖体图谱","生物膜","枯草芽孢杆菌"],"selected":0,"story_id":null,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"crossref-cns","source_name":"Crossref · CNS 与大子刊新上线（领域过滤）","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"sci-adv","journal_tier":"cns-sub","journal_if":11.7,"is_mock":false,"summary_zh":"该研究在枯草芽孢杆菌中揭示应激信号与密码子特异性翻译调控之间的直接联系：警戒信号分子 ppGpp 直接抑制保守的 tRNA 修饰 GTPase MnmE（TrmE），后者负责摆动尿苷的甲氨基甲基（mnm）修饰。高分辨核糖体图谱显示，缺失 MnmE 会使核糖体在 AAG 密码子处暂停增加，并重编程部分基因（含小开放阅读框）的翻译；其中包括一个此前未被识别的富 AAG 前导肽，它控制生物膜抑制因子 AbrB 的表达。mnmE 突变体表现为组成型胞外基质产生，并可绕过 relA 突变体的生物膜缺陷。研究由此建立了一条连接 ppGpp 信号、tRNA 修饰、密码子特异性翻译与多细胞发育的通路。","summary":"Transfer RNA (tRNA) modifications influence decoding efficiency and translational fidelity, yet how they are integrated into bacterial signaling networks remains poorly understood. Here, we identify a direct connection between stress signaling and codon-specific translational regulation. We show that the alarmone guanosine tetraphosphate (ppGpp) directly inhibits MnmE (TrmE), a conserved tRNA-modification GTPase required for methylaminomethyl (mnm) modification of wobble uridine. High-resolution ribosome profiling in Bacillus subtilis revealed that loss of MnmE selectively increases ribosome pausing at AAG codons and reprograms translation of a subset of genes, including small open reading frames. Among these is a previously unrecognized AAG-containing leader peptide that controls expression of the biofilm repressor AbrB. Consistent with this mechanism, mnmE mutants exhibit constitutive extracellular matrix production and bypass the biofilm defect of a relA mutant. Together, these findings establish a pathway linking ppGpp signaling, tRNA modification, codon-specific translation, and multicellular development.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}