mir-233 modulates the unfolded protein response in C. elegans during Pseudomonas aeruginosa infection.

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 resp...

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Main Authors: Li-Li Dai, Jin-Xia Gao, Cheng-Gang Zou, Yi-Cheng Ma, Ke-Qin Zhang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS Pathogens
Online Access:http://europepmc.org/articles/PMC4287614?pdf=render
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author Li-Li Dai
Jin-Xia Gao
Cheng-Gang Zou
Yi-Cheng Ma
Ke-Qin Zhang
author_facet Li-Li Dai
Jin-Xia Gao
Cheng-Gang Zou
Yi-Cheng Ma
Ke-Qin Zhang
author_sort Li-Li Dai
collection DOAJ
description 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.
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spelling doaj.art-8d0493a5555c4efc9f6f09e655277c132022-12-21T22:52:08ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742015-01-01111e100460610.1371/journal.ppat.1004606mir-233 modulates the unfolded protein response in C. elegans during Pseudomonas aeruginosa infection.Li-Li DaiJin-Xia GaoCheng-Gang ZouYi-Cheng MaKe-Qin ZhangThe 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.http://europepmc.org/articles/PMC4287614?pdf=render
spellingShingle Li-Li Dai
Jin-Xia Gao
Cheng-Gang Zou
Yi-Cheng Ma
Ke-Qin Zhang
mir-233 modulates the unfolded protein response in C. elegans during Pseudomonas aeruginosa infection.
PLoS Pathogens
title mir-233 modulates the unfolded protein response in C. elegans during Pseudomonas aeruginosa infection.
title_full mir-233 modulates the unfolded protein response in C. elegans during Pseudomonas aeruginosa infection.
title_fullStr mir-233 modulates the unfolded protein response in C. elegans during Pseudomonas aeruginosa infection.
title_full_unstemmed mir-233 modulates the unfolded protein response in C. elegans during Pseudomonas aeruginosa infection.
title_short mir-233 modulates the unfolded protein response in C. elegans during Pseudomonas aeruginosa infection.
title_sort mir 233 modulates the unfolded protein response in c elegans during pseudomonas aeruginosa infection
url http://europepmc.org/articles/PMC4287614?pdf=render
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