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Title: Analysis of host microRNA function uncovers a role for miR-29b-2-5p in Shigella capture by filopodia
Authors: Sunkavalli, Ushasree
Aguilar, Carmen
Silva, Ricardo Jorge 
Sharan, Malvika
Cruz, Ana Rita 
Tawk, Caroline
Maudet, Claire
Mano, Miguel 
Eulálio, Ana 
Issue Date: Apr-2017
Publisher: Public Library of Science
Project: FCT Investigator Programme IF/00694/2013 
Bavarian Ministry of Sciences, Research and the Arts in the framework of the Bavarian Molecular Biosystems Research Network (BioSysNet to AE) 
German Research Foundation DFG project BR 4837/1-1 
German Research Foundation (DFG) and the University of Wuerzburg in the funding programme Open Access Publishing 
Serial title, monograph or event: PLoS Pathogens
Volume: 13
Issue: 4
Abstract: MicroRNAs play an important role in the interplay between bacterial pathogens and host cells, participating as host defense mechanisms, as well as exploited by bacteria to subvert host cellular functions. Here, we show that microRNAs modulate infection by Shigella flexneri, a major causative agent of bacillary dysentery in humans. Specifically, we characterize the dual regulatory role of miR-29b-2-5p during infection, showing that this microRNA strongly favors Shigella infection by promoting both bacterial binding to host cells and intracellular replication. Using a combination of transcriptome analysis and targeted high-content RNAi screening, we identify UNC5C as a direct target of miR-29b-2-5p and show its pivotal role in the modulation of Shigella binding to host cells. MiR-29b-2-5p, through repression of UNC5C, strongly enhances filopodia formation thus increasing Shigella capture and promoting bacterial invasion. The increase of filopodia formation mediated by miR-29b-2-5p is dependent on RhoF and Cdc42 Rho-GTPases. Interestingly, the levels of miR-29b-2-5p, but not of other mature microRNAs from the same precursor, are decreased upon Shigella replication at late times post-infection, through degradation of the mature microRNA by the exonuclease PNPT1. While the relatively high basal levels of miR-29b-2-5p at the start of infection ensure efficient Shigella capture by host cell filopodia, dampening of miR-29b-2-5p levels later during infection may constitute a bacterial strategy to favor a balanced intracellular replication to avoid premature cell death and favor dissemination to neighboring cells, or alternatively, part of the host response to counteract Shigella infection. Overall, these findings reveal a previously unappreciated role of microRNAs, and in particular miR-29b-2-5p, in the interaction of Shigella with host cells.
ISSN: 1553-7374
DOI: 10.1371/journal.ppat.1006327
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais

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