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新型癌症相关微生物具核梭杆菌的 RNA 全景图。

RNA landscape of the emerging cancer-associated microbe Fusobacterium nucleatum.

机构信息

Helmholtz Institute for RNA-based Infection Research, Helmholtz Centre for Infection Research, Würzburg, Germany.

Institute for Molecular Infection Biology, University of Würzburg, Würzburg, Germany.

出版信息

Nat Microbiol. 2021 Aug;6(8):1007-1020. doi: 10.1038/s41564-021-00927-7. Epub 2021 Jul 8.

Abstract

Fusobacterium nucleatum, long known as a constituent of the oral microflora, has recently garnered renewed attention for its association with several different human cancers. The growing interest in this emerging cancer-associated bacterium contrasts with a paucity of knowledge about its basic gene expression features and physiological responses. As fusobacteria lack all established small RNA-associated proteins, post-transcriptional networks in these bacteria are also unknown. In the present study, using differential RNA-sequencing, we generate high-resolution global RNA maps for five clinically relevant fusobacterial strains-F. nucleatum subspecies nucleatum, animalis, polymorphum and vincentii, as well as F. periodonticum-for early, mid-exponential growth and early stationary phase. These data are made available in an online browser, and we use these to uncover fundamental aspects of fusobacterial gene expression architecture and a suite of non-coding RNAs. Developing a vector for functional analysis of fusobacterial genes, we discover a conserved fusobacterial oxygen-induced small RNA, FoxI, which serves as a post-transcriptional repressor of the major outer membrane porin FomA. Our findings provide a crucial step towards delineating the regulatory networks enabling F. nucleatum adaptation to different environments, which may elucidate how these bacteria colonize different compartments of the human body.

摘要

具核梭杆菌,长期以来被认为是口腔微生物群的组成部分,最近因其与几种不同的人类癌症有关而引起了新的关注。人们对这种新兴的与癌症相关的细菌越来越感兴趣,而对其基本基因表达特征和生理反应的了解却很少。由于梭杆菌缺乏所有已建立的与小 RNA 相关的蛋白质,因此这些细菌中的转录后网络也未知。在本研究中,我们使用差异 RNA 测序,为五种临床相关的梭杆菌菌株 - 具核梭杆菌亚种、动物亚种、多形亚种和文森特亚种,以及牙周梭杆菌,生成了早期、中期指数生长和早期静止期的高分辨率全局 RNA 图谱。这些数据可在在线浏览器中获得,我们利用这些数据揭示了梭杆菌基因表达架构和一系列非编码 RNA 的基本方面。我们开发了一种用于功能性分析梭杆菌基因的载体,发现了一种保守的梭杆菌氧诱导小 RNA FoxI,它作为主要外膜孔蛋白 FomA 的转录后抑制剂。我们的发现为描绘使具核梭杆菌适应不同环境的调控网络提供了重要的一步,这可能阐明了这些细菌如何定植人体的不同部位。

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