A subcellular map of translational machinery composition and regulation at the single-molecule level.

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2025-03-07 DOI:10.1126/science.adn2623

Zijian Zhang, Adele Xu, Yunhao Bai, Yuxiang Chen, Kitra Cates, Craig Kerr, Abel Bermudez, Teodorus Theo Susanto, Kelsie Wysong, Fernando J García Marqués, Garry P Nolan, Sharon Pitteri, Maria Barna

{"title":"A subcellular map of translational machinery composition and regulation at the single-molecule level.","authors":"Zijian Zhang, Adele Xu, Yunhao Bai, Yuxiang Chen, Kitra Cates, Craig Kerr, Abel Bermudez, Teodorus Theo Susanto, Kelsie Wysong, Fernando J García Marqués, Garry P Nolan, Sharon Pitteri, Maria Barna","doi":"10.1126/science.adn2623","DOIUrl":null,"url":null,"abstract":"Millions of ribosomes are packed within mammalian cells, yet we lack tools to visualize them in toto and characterize their subcellular composition. In this study, we present ribosome expansion microscopy (RiboExM) to visualize individual ribosomes and an optogenetic proximity-labeling technique (ALIBi) to probe their composition. We generated a super-resolution ribosomal map, revealing subcellular translational hotspots and enrichment of 60S subunits near polysomes at the endoplasmic reticulum (ER). We found that Lsg1 tethers 60S to the ER and regulates translation of select proteins. Additionally, we discovered ribosome heterogeneity at mitochondria guiding translation of metabolism-related transcripts. Lastly, we visualized ribosomes in neurons, revealing a dynamic switch between monosomes and polysomes in neuronal translation. Together, these approaches enable exploration of ribosomal localization and composition at unprecedented resolution.","PeriodicalId":21678,"journal":{"name":"Science","volume":"387 6738","pages":"eadn2623"},"PeriodicalIF":44.7000,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1126/science.adn2623","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Millions of ribosomes are packed within mammalian cells, yet we lack tools to visualize them in toto and characterize their subcellular composition. In this study, we present ribosome expansion microscopy (RiboExM) to visualize individual ribosomes and an optogenetic proximity-labeling technique (ALIBi) to probe their composition. We generated a super-resolution ribosomal map, revealing subcellular translational hotspots and enrichment of 60S subunits near polysomes at the endoplasmic reticulum (ER). We found that Lsg1 tethers 60S to the ER and regulates translation of select proteins. Additionally, we discovered ribosome heterogeneity at mitochondria guiding translation of metabolism-related transcripts. Lastly, we visualized ribosomes in neurons, revealing a dynamic switch between monosomes and polysomes in neuronal translation. Together, these approaches enable exploration of ribosomal localization and composition at unprecedented resolution.

查看原文本刊更多论文

在单分子水平上翻译机制组成和调控的亚细胞图谱。

哺乳动物细胞中有数百万个核糖体，但我们缺乏将它们全部可视化并表征其亚细胞组成的工具。在这项研究中，我们提出了核糖体扩增显微镜（RiboExM）来观察单个核糖体和光遗传接近标记技术（ALIBi）来探测它们的组成。我们绘制了一幅超分辨率核糖体图，揭示了亚细胞翻译热点和内质网（ER）多聚体附近60S亚基的富集。我们发现Lsg1将60S连接到内质网并调节选定蛋白的翻译。此外，我们发现线粒体的核糖体异质性指导代谢相关转录物的翻译。最后，我们可视化了神经元中的核糖体，揭示了神经元翻译中单体和多体之间的动态切换。总之，这些方法能够以前所未有的分辨率探索核糖体的定位和组成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

期刊介绍： Science is a leading outlet for scientific news, commentary, and cutting-edge research. Through its print and online incarnations, Science reaches an estimated worldwide readership of more than one million. Science’s authorship is global too, and its articles consistently rank among the world's most cited research. Science serves as a forum for discussion of important issues related to the advancement of science by publishing material on which a consensus has been reached as well as including the presentation of minority or conflicting points of view. Accordingly, all articles published in Science—including editorials, news and comment, and book reviews—are signed and reflect the individual views of the authors and not official points of view adopted by AAAS or the institutions with which the authors are affiliated. Science seeks to publish those papers that are most influential in their fields or across fields and that will significantly advance scientific understanding. Selected papers should present novel and broadly important data, syntheses, or concepts. They should merit recognition by the wider scientific community and general public provided by publication in Science, beyond that provided by specialty journals. Science welcomes submissions from all fields of science and from any source. The editors are committed to the prompt evaluation and publication of submitted papers while upholding high standards that support reproducibility of published research. Science is published weekly; selected papers are published online ahead of print.