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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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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. |
format | Online Article Text |
id | pubmed-5398735 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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