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The human-specific miR-6762-5p is an activator of RhoA GTPase enhancing Shigella flexneri intercellular spreading

Reisacher, C.; Saifi, E.; Ageron-Ardila, E.; Mallmann, R. T.; Klugbauer, N.; Skurnik, D.; Arbibe, L.

2022-11-28 microbiology
10.1101/2022.11.28.518194 bioRxiv
Show abstract

MicroRNAs have recently emerged as major players in host-bacterial pathogens interaction, 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 evolutionary emerged 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 fibers 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. Overall, we have identified a human-specific miR-6762-5p acting specifically at the Shigella dissemination step. 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.

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