Bacterial Infection & RNA Destiny Group, Institut de biologie de l'ENS (IBENS), École normale supérieure, CNRS, INSERM, Université PSL , Paris, France.
Computational Biology and Bioinformatics Group, Institut de biologie de l'ENS (IBENS), École normale supérieure, CNRS, INSERM, Université PSL , Paris, France.
RNA Biol. 2020 Oct;17(10):1492-1507. doi: 10.1080/15476286.2020.1777380. Epub 2020 Jun 25.
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 , 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 5'-terminal oligopyrimidine motif. Pre-silencing the most repressed target gene () slowed down the intracellular multiplication of , suggesting that the infected host cell can benefit from the repression of genes involved in protein synthesis and thereby better control infection.
细胞内细菌病原体对哺乳动物细胞的入侵会重新排列其基因表达和功能;然而,我们缺乏对塑造宿主反应的不同控制水平的动态洞察。在这里,我们使用转录组分析和核糖体分析,在人类肠道上皮细胞被流行株感染的时间过程中,研究了转录和翻译调控各自的贡献。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因素。翻译抑制并没有广泛但短暂的关闭,而是特异性且持久地影响了编码含有 5'端寡嘧啶基序的翻译机制成分的转录本。预先沉默受抑制最严重的靶基因()减缓了细胞内的繁殖,这表明感染的宿主细胞可以从抑制参与蛋白质合成的基因中受益,从而更好地控制感染。