Salmonella produce microRNA-like RNA fragment Sal-1 in the infected cells to facilitate intracellular survival.

Salmonella produce microRNA-like RNA fragment Sal-1 in the infected cells to facilitate intracellular survival.
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沙门氏菌在受感染的细胞中产生类似 microRNA 的 RNA 片段 Sal-1 以促进细胞内存活

DOI:
10.1038/s41598-017-02669-1
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发表时间:
2017-05-24
期刊:
影响因子:
4.6
通讯作者:
Zen K
Zen K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Gu H;Zhao C;Zhang T;Liang H;Wang XM;Pan Y;Chen X;Zhao Q;Li D;Liu F;Zhang CY;Zen K

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沙门氏菌已经发展出一种复杂的机制来逃避免疫清除并促进受感染细胞的存活。以往的研究大多集中在细菌本身或宿主细胞上,宿主-病原体相互作用的机制有待进一步探讨。在本研究中,我们发现沙门氏菌可以利用哺乳动物细胞的非经典microRNA加工机制,进一步将细菌的小非编码RNA加工成microRNA样片段。Sal-1是感染细胞中拷贝数最高的片段之一,来源于沙门氏菌核糖体RNA转录物的5′-前导序列,具有含“茎”结构的前体。Sal-1前体向成熟Sal-1的加工依赖于宿主细胞Argonaute 2(AGO 2)而不是Dicer。在功能上,消耗细胞Sal-1强烈地使沙门氏菌对体外和体内宿主防御的抗性降低。总之,我们展示了沙门氏菌逃避宿主免疫清除的新策略,其中沙门氏菌产生microRNA样功能性RNA片段以建立促进细菌存活的微环境。
Salmonella have developed a sophisticated machinery to evade immune clearance and promote survival in the infected cells. Previous studies were mostly focused on either bacteria itself or host cells, the interaction mechanism of host-pathogen awaits further exploration. In the present study, we show that Salmonella can exploit mammalian cell non-classical microRNA processing machinery to further process bacterial small non-coding RNAs into microRNA-like fragments. Sal-1, one such fragment with the highest copy number in the infected cells, is derived from Salmonella 5′-leader of the ribosomal RNA transcript and has a ‘stem’ structure-containing precursor. Processing of Sal-1 precursors to mature Sal-1 is dependent on host cell Argonaute 2 (AGO2) but not Dicer. Functionally, depleting cellular Sal-1 strongly renders the Salmonella bacteria less resistant to the host defenses both in vitro and in vivo. In conclusion, we demonstrate a novel strategy for Salmonella evading the host immune clearance, in which Salmonella produce microRNA-like functional RNA fragments to establish a microenvironment facilitating bacterial survival.