麻省理工学院Jonathan S. Weissman课题组取得一项新突破。他们发现了邻近特异性核糖体分析揭示了局部线粒体翻译的逻辑。相关论文发表在2025年8月27日出版的《细胞》杂志上。
研究团队提出了用于翻译定位的LOV结构域控制连接酶（LOCL-TL），这是一种在生理条件下监测任何特定亚细胞位置密码子解析翻译的光遗传学方法。LOCL-TL在线粒体定位翻译中的应用表明，约20%的人类核编码线粒体基因在线粒体外膜（OMM）上翻译。线粒体翻译信息根据编码蛋白长度、募集机制和细胞功能分为两类。一种进化上古老的机制允许新生链通过意想不到的两部分靶向信号驱动长蛋白的共翻译招募。相反，短蛋白的mRNA，特别是真核起源的电子传递链（ETC）成分，被OMM蛋白A激酶锚定蛋白1（AKAP1）以依赖mRNA剪接的翻译无关的方式特异性募集。AKAP1缺失降低ETC水平。LOCL-TL揭示了一种分层策略，可以优先翻译OMM上的一组蛋白质。
据介绍，本地化翻译广泛地实现了基因表达的时空控制。
附：英文原文
Title: Proximity-specific ribosome profiling reveals the logic of localized mitochondrial translation
Author: Jingchuan Luo, Stuti Khandwala, Jingjie Hu, Song-Yi Lee, Kelsey L. Hickey, Zebulon G. Levine, J. Wade Harper, Alice Y. Ting, Jonathan S. Weissman
Issue&Volume: 2025-08-27
Abstract: Localized translation broadly enables spatiotemporal control of gene expression. Here, we present LOV-domain-controlled ligase for translation localization (LOCL-TL), an optogenetic approach for monitoring translation with codon resolution at any defined subcellular location under physiological conditions. Application of LOCL-TL to mitochondrially localized translation revealed that ～20% of human nuclear-encoded mitochondrial genes are translated on the outer mitochondrial membrane (OMM). Mitochondrially translated messages form two classes distinguished by encoded protein length, recruitment mechanism, and cellular function. An evolutionarily ancient mechanism allows nascent chains to drive cotranslational recruitment of long proteins via an unanticipated bipartite targeting signal. Conversely, mRNAs of short proteins, especially eukaryotic-origin electron transport chain (ETC) components, are specifically recruited by the OMM protein A-kinase anchoring protein 1 (AKAP1) in a translation-independent manner that depends on mRNA splicing. AKAP1 loss lowers ETC levels. LOCL-TL thus reveals a hierarchical strategy that enables preferential translation of a subset of proteins on the OMM.
DOI: 10.1016/j.cell.2025.08.002
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00916-X