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Published on: September 9, 2014
The Human-Specific miR-6762-5p Is an Activator of RhoA GTPase Enhancing Shigella flexneri Intercellular Spreading
Caroline Reisacher1, Estelle Saifi1, Elisabeth Ageron1
1Université Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, Paris, France.
Abstract:
MicroRNAs have recently emerged as major players in host -bacterial pathogen interactions, either as part of the host defense mechanism to neutralize infection or as a bacterial arsenal aimed at subverting host cell functions. Here, we identify the newly evolved human microRNA miR-6762-5p as a new player in the host-Shigella interplay. A microarray analysis in infected epithelial cells allowed the detection of this miRNA exclusively during the late phase of infection. Conditional expression of miR-6762-5p combined with a transcriptome analysis indicated a role in cytoskeleton remodeling. Likewise, miR-6762-5p enhanced stress fiber formation through RhoA activation, and in silico analysis identified several regulators of RhoA activity as potential direct transcriptional targets. We further showed that miR-6762-5p expression induces an increase in Shigella intercellular spreading, while miR-6762-5p inhibition reduced bacterial dissemination. We propose a model in which the expression of miR-6762-5p induces cytoskeleton modifications through RhoA activation to achieve a successful dissemination of Shigella in the host.
Insights
Newly discovered microRNA miR-6762-5p promotes Shigella infection by remodeling the host cytoskeleton. Inhibition of this microRNA reduces bacterial spread, offering a potential target for controlling Shigella dissemination.
Area of Science:
- Microbiology
- Molecular Biology
- Immunology
Background:
- MicroRNAs (miRNAs) are key regulators in host-pathogen interactions.
- They can either support host defense or be exploited by pathogens.
- The role of specific miRNAs in Shigella infection is an active area of research.
Purpose of the Study:
- To identify novel microRNAs involved in host-Shigella interplay.
- To elucidate the function of the newly evolved human microRNA miR-6762-5p in Shigella infection.
- To understand the mechanism by which miR-6762-5p influences bacterial dissemination.
Main Methods:
- Microarray analysis of infected epithelial cells to detect differentially expressed miRNAs.
- Conditional expression of miR-6762-5p and subsequent transcriptome analysis.
- Assessment of cytoskeleton remodeling, RhoA activation, and bacterial intercellular spreading.
- In silico analysis to identify potential miRNA targets.
Main Results:
- miR-6762-5p was exclusively detected during the late phase of Shigella infection.
- miR-6762-5p expression promoted stress fiber formation via RhoA activation and cytoskeleton remodeling.
- In silico analysis identified RhoA regulators as potential targets of miR-6762-5p.
- miR-6762-5p expression enhanced Shigella intercellular spreading, while its inhibition reduced dissemination.
Conclusions:
- The newly evolved human microRNA miR-6762-5p is a significant factor in host-Shigella interactions.
- miR-6762-5p facilitates Shigella dissemination by modulating host cytoskeleton dynamics through RhoA activation.
- Targeting miR-6762-5p may represent a novel therapeutic strategy against Shigella infections.
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