The human-specific miR-6762-5p is an activator of RhoA GTPase enhancingShigella flexneriintercellular spreading

Abstract

AbstractMicroRNAs 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-Shigellainterplay. 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 andin silicoanalysis identified several regulators of RhoA activity as potential direct transcriptional targets. We further showed that miR-6762-5p expression induces an increase inShigellaintercellular spreading, while miR-6762-5p inhibition reduced bacterial dissemination. Overall, we have identified a human-specific miR-6762-5p acting specifically at theShigelladissemination step. We propose a model in which the expression of miR-6762-5p induces cytoskeleton modifications through RhoA activation to achieve a successful dissemination ofShigellain the host.