ENSURE: the encyclopedia of suppressor tRNA with an AI assistant

作者：Z. Ouyang, Yifeng Zhang, Fan Feng, Xudong Zeng, Qiong Wu, Abdul Hafeez, Wenkai Teng, Yixin Kong, Xiaoning Bu, Yang Sun, Bin Li, Yan‐Zi Wen, Zhao‐Rong Lun, Liang‐Hu Qu, Xiao Feng, Ling‐Ling Zheng · 发表于：Nucleic Acids Research · 年份：2025 · DOI：10.1093/nar/gkaf1062 · 被引用次数：2 · 研究领域：RNA modifications and cancer、RNA and protein synthesis mechanisms、Bacterial Genetics and Biotechnology

Suppressor transfer RNAs (sup-tRNAs) offer a promising strategy for rescuing proteins truncated by premature termination codons via translational readthrough. Despite recent advances in genetic code expansion and RNA therapeutics that have facilitated sup-tRNA engineering, progress remains constrained by the lack of a dedicated, integrative data platform. Here, we present ENSURE (https://trna.lumoxuan.cn/), a comprehensive knowledge base that aggregates 2152 disease- and cancer-associated nonsense, missense, and frameshift variants; 86 experimentally validated natural sup-tRNAs, 1108 tRNA engineering strategies; and 487 curated tRNA element records. All sequences undergo multiple sequence alignment, secondary structure prediction, and AlphaFold 3 modeling accompanied by interactive 2D/3D visualization. ENSURE supports keyword and BLAST searches, as well as bulk downloads. A key feature is an AI assistant based on a retrieval-augmented generation architecture: ~123.7k tokens of database pages, literature abstracts, structural annotations, and other resources are chunked and encoded with Sentence-BERT; user queries are processed similarly, matched to relevant chunks, concatenated with the query, and passed to a large language model to generate answers with illustrative resources inserted automatically. By combining curated data, structural models, and an interactive AI assistant, ENSURE provides a powerful platform to accelerate sup-tRNA research and translational applications.