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Analysis of host microRNA function uncovers a role for miR-29b-2-5p in Shigella capture by filopodia

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 o...

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Autores principales: Sunkavalli, Ushasree, Aguilar, Carmen, Silva, Ricardo Jorge, Sharan, Malvika, Cruz, Ana Rita, Tawk, Caroline, Maudet, Claire, Mano, Miguel, Eulalio, Ana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5398735/
https://www.ncbi.nlm.nih.gov/pubmed/28394930
http://dx.doi.org/10.1371/journal.ppat.1006327
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author Sunkavalli, Ushasree
Aguilar, Carmen
Silva, Ricardo Jorge
Sharan, Malvika
Cruz, Ana Rita
Tawk, Caroline
Maudet, Claire
Mano, Miguel
Eulalio, Ana
author_facet Sunkavalli, Ushasree
Aguilar, Carmen
Silva, Ricardo Jorge
Sharan, Malvika
Cruz, Ana Rita
Tawk, Caroline
Maudet, Claire
Mano, Miguel
Eulalio, Ana
author_sort Sunkavalli, Ushasree
collection PubMed
description 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.
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spelling pubmed-53987352017-05-14 Analysis of host microRNA function uncovers a role for miR-29b-2-5p in Shigella capture by filopodia Sunkavalli, Ushasree Aguilar, Carmen Silva, Ricardo Jorge Sharan, Malvika Cruz, Ana Rita Tawk, Caroline Maudet, Claire Mano, Miguel Eulalio, Ana PLoS Pathog Research Article 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. Public Library of Science 2017-04-10 /pmc/articles/PMC5398735/ /pubmed/28394930 http://dx.doi.org/10.1371/journal.ppat.1006327 Text en © 2017 Sunkavalli et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Sunkavalli, Ushasree
Aguilar, Carmen
Silva, Ricardo Jorge
Sharan, Malvika
Cruz, Ana Rita
Tawk, Caroline
Maudet, Claire
Mano, Miguel
Eulalio, Ana
Analysis of host microRNA function uncovers a role for miR-29b-2-5p in Shigella capture by filopodia
title Analysis of host microRNA function uncovers a role for miR-29b-2-5p in Shigella capture by filopodia
title_full Analysis of host microRNA function uncovers a role for miR-29b-2-5p in Shigella capture by filopodia
title_fullStr Analysis of host microRNA function uncovers a role for miR-29b-2-5p in Shigella capture by filopodia
title_full_unstemmed Analysis of host microRNA function uncovers a role for miR-29b-2-5p in Shigella capture by filopodia
title_short Analysis of host microRNA function uncovers a role for miR-29b-2-5p in Shigella capture by filopodia
title_sort analysis of host microrna function uncovers a role for mir-29b-2-5p in shigella capture by filopodia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5398735/
https://www.ncbi.nlm.nih.gov/pubmed/28394930
http://dx.doi.org/10.1371/journal.ppat.1006327
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