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Coordination of transcriptional and translational regulations in human epithelial cells infected by Listeria monocytogenes.
RNA Biology ( IF 4.1 ) Pub Date : 2020-06-25 , DOI: 10.1080/15476286.2020.1777380
Vinko Besic 1 , Fatemeh Habibolahi 1, 2 , Benoît Noël 1, 2 , Sebastian Rupp 1 , Auguste Genovesio 2 , Alice Lebreton 1, 3
Affiliation  

The invasion of mammalian cells by intracellular bacterial pathogens reshuffles their gene expression and functions; however, we lack dynamic insight into the distinct control levels that shape the host response. Here, we have addressed the respective contribution of transcriptional and translational regulations during a time-course of infection of human intestinal epithelial cells by an epidemic strain of Listeria monocytogenes, using transcriptome analysis paralleled with ribosome profiling. Upregulations were dominated by early transcriptional activation of pro-inflammatory genes, whereas translation inhibition appeared as the major driver of downregulations. Instead of a widespread but transient shutoff, translation inhibition affected specifically and durably transcripts encoding components of the translation machinery harbouring a 5ʹ-terminal oligopyrimidine motif. Pre-silencing the most repressed target gene (PABPC1) slowed down the intracellular multiplication of Listeria monocytogenes, suggesting that the infected host cell can benefit from the repression of genes involved in protein synthesis and thereby better control infection.



中文翻译:

在单核细胞增生性李斯特菌感染的人类上皮细胞中转录和翻译规则的协调。

细胞内细菌病原体对哺乳动物细胞的入侵改变了它们的基因表达和功能。但是,我们缺乏动态了解形成宿主反应的不同控制水平。在这里,我们已经解决了由单核细胞增生李斯特菌流行株感染人肠道上皮细胞的时间过程中转录和翻译规则的各自贡献,同时使用转录组分析和核糖体分析。上调主要由促炎基因的早期转录激活主导,而翻译抑制似乎是下调的主要驱动力。代替普遍但短暂的关闭,翻译抑制作用特异性地和持久地影响编码具有5′-末端寡嘧啶基序的翻译机器的组分的转录物。将沉默最强的目标基因(PABPC1)预沉默会减慢单核细胞增生李斯特菌的细胞内增殖,这表明受感染的宿主细胞可受益于蛋白合成相关基因的抑制,从而更好地控制感染。

更新日期:2020-08-31
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