Dual RNA-seq unveils noncoding RNA functions in host-pathogen interactions
Dual RNA-seq unveils noncoding RNA functions in host-pathogen interactions
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DOI：
10.1038/nature16547
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发表时间：
2016-01-28
期刊：
影响因子：
64.8
通讯作者：
Vogel, Joerg
中科院分区：
文献类型：
--
作者：
Westermann, Alexander J.;Foerstner, Konrad U.;Vogel, Joerg
细菌表达许多小RNA，由于在标准毒力测定中缺乏稳健的表型，因此对这些小RNA在发病机制中的调节作用仍然知之甚少。在这里，我们使用一个通用的“双RNA-seq”的方法，同时在病原体和宿主沙门氏菌血清型鼠伤寒沙门氏菌感染期间的RNA表达谱，并揭示细菌核糖核酸调节子的分子影响。我们确定了一个PhoP激活的小RNA，PinT，细菌内化后，暂时控制细胞内生存所需的入侵相关的效应子和毒力基因的表达。这种核糖核酸调节活性引起宿主的编码和非编码转录物的普遍变化。种间相关性分析将PinT与宿主细胞JAK-STAT信号联系起来，我们确定了多个长非编码RNA中的感染特异性改变。我们的研究为细胞内细菌病原体及其宿主的灵敏的基于RNA的分析提供了一个范例，而无需物理分离，以及病原体基因隐藏功能的新发现途径。
Bacteria express many small RNAs for which the regulatory roles in pathogenesis have remained poorly understood due to a paucity of robust phenotypes in standard virulence assays. Here we use a generic 'dual RNA-seq' approach to profile RNA expression simultaneously in pathogen and host during Salmonella enterica serovar Typhimurium infection and reveal the molecular impact of bacterial riboregulators. We identify a PhoP-activated small RNA, PinT, which upon bacterial internalization temporally controls the expression of both invasion-associated effectors and virulence genes required for intracellular survival. This riboregulatory activity causes pervasive changes in coding and noncoding transcripts of the host. Interspecies correlation analysis links PinT to host cell JAK-STAT signalling, and we identify infection-specific alterations in multiple long noncoding RNAs. Our study provides a paradigm for a sensitive RNA-based analysis of intracellular bacterial pathogens and their hosts without physical separation, as well as a new discovery route for hidden functions of pathogen genes.