mir-233 Modulates the Unfolded Protein Response in C. elegans during Pseudomonas aeruginosa Infection

PLoS Pathogens

Ke-Qin Zhang¹  Cheng-Gang Zou¹  Li-Li Dai¹  Jin-Xia Gao¹  Yi-Cheng Ma¹ 

[1] Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming, Yunnan, China

关键词: Pseudomonas aeruginosa;    MicroRNAs;    RNA interference;    Innate immune system;    Caenorhabditis elegans;    Immune response;    Gene expression;    RNA sequencing;   

DOI  :  10.1371/journal.ppat.1004606

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The unfolded protein response (UPR), which is activated by perturbations of the endoplasmic reticulum homeostasis, has been shown to play an important role in innate immunity and inflammation. However, little is known about the molecular mechanisms underlying activation of the UPR during immune responses. Using small RNA deep sequencing and reverse genetic analysis, we show that the microRNA mir-233 is required for activation of the UPR in Caenorhabditis elegans exposed to Pseudomonas aeruginosa PA14. P. aeruginosa infection up-regulates the expression of mir-233 in a p38 MAPK-dependent manner. Quantitative proteomic analysis identifies SCA-1, a C. elegans homologue of the sarco/endoplasmic reticulum Ca2+-ATPase, as a target of mir-233. During P. aeruginosa PA14 infection, mir-233 represses the protein levels of SCA-1, which in turn leads to activation of the UPR. Whereas mir-233 mutants are more sensitive to P. aeruginosa infection, knockdown of sca-1 leads to enhanced resistance to the killing by P. aeruginosa. Our study indicates that microRNA-dependent pathways may have an impact on innate immunity by activating the UPR.

【 授权许可】

CC BY