A non-canonical RNAi pathway controls virulence and genome stability in Mucorales.

Epimutations in fungal pathogens are emerging as novel phenomena that could explain the fast-developing resistance to antifungal drugs and other stresses. These epimutations are generated by RNA interference (RNAi) mechanisms that transiently silence specific genes to overcome stressful stimuli. The...

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Autores: Pérez Arques, Carlos, Navarro Mendoza, María Isabel, Murcia Flores, Laura, Navarro, Eusebio, Garre, Victoriano, Nicolás, Francisco Esteban
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad Católica San Antonio de Murcia (UCAM)
Repositorio:RIUCAM. Repositorio Institucional de la Universidad Católica San Antonio de Murcia
OAI Identifier:oai:repositorio.ucam.edu:10952/7200
Acceso en línea:http://hdl.handle.net/10952/7200
Access Level:acceso abierto
Palabra clave:Epimutations
Mucor circinelloides
RNA interference
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spelling A non-canonical RNAi pathway controls virulence and genome stability in Mucorales.Pérez Arques, CarlosNavarro Mendoza, María IsabelMurcia Flores, LauraNavarro, EusebioGarre, VictorianoNicolás, Francisco EstebanEpimutationsMucor circinelloidesRNA interferenceEpimutations in fungal pathogens are emerging as novel phenomena that could explain the fast-developing resistance to antifungal drugs and other stresses. These epimutations are generated by RNA interference (RNAi) mechanisms that transiently silence specific genes to overcome stressful stimuli. The early-diverging fungus Mucor circinelloides exercises a fine control over two interacting RNAi pathways to produce epimutants: the canonical RNAi pathway and a new RNAi degradative pathway. The latter is considered a non-canonical RNAi pathway (NCRIP) because it relies on RNA-dependent RNA polymerases (RdRPs) and a novel ribonuclease III-like named R3B2 to degrade target transcripts. Here in this work, we uncovered the role of NCRIP in regulating virulence processes and transposon movements through key components of the pathway, RdRP1 and R3B2. Mutants in these genes are unable to launch a proper virulence response to macrophage phagocytosis, resulting in a decreased virulence potential. The transcriptomic profile of rdrp1Δ and r3b2Δ mutants revealed a pre-exposure adaptation to the stressful phagosomal environment even when the strains are not confronted by macrophages. These results suggest that NCRIP represses key targets during regular growth and releases its control when a stressful environment challenges the fungus. NCRIP interacts with the RNAi canonical core to protect genome stability by controlling the expression of centromeric retrotransposable elements. In the absence of NCRIP, these retrotransposons are robustly repressed by the canonical RNAi machinery; thus, supporting the antagonistic role of NCRIP in containing the epimutational pathway. Both interacting RNAi pathways might be essential to govern host-pathogen interactions through transient adaptations, contributing to the unique traits of the emerging infection mucormycosis.Medicina2020info:eu-repo/semantics/articlehttp://hdl.handle.net/10952/7200reponame:RIUCAM. Repositorio Institucional de la Universidad Católica San Antonio de Murciainstname:Universidad Católica San Antonio de Murcia (UCAM)Inglésinfo:eu-repo/semantics/openAccessoai:repositorio.ucam.edu:10952/72002026-06-07T18:35:21Z
dc.title.none.fl_str_mv A non-canonical RNAi pathway controls virulence and genome stability in Mucorales.
title A non-canonical RNAi pathway controls virulence and genome stability in Mucorales.
spellingShingle A non-canonical RNAi pathway controls virulence and genome stability in Mucorales.
Pérez Arques, Carlos
Epimutations
Mucor circinelloides
RNA interference
title_short A non-canonical RNAi pathway controls virulence and genome stability in Mucorales.
title_full A non-canonical RNAi pathway controls virulence and genome stability in Mucorales.
title_fullStr A non-canonical RNAi pathway controls virulence and genome stability in Mucorales.
title_full_unstemmed A non-canonical RNAi pathway controls virulence and genome stability in Mucorales.
title_sort A non-canonical RNAi pathway controls virulence and genome stability in Mucorales.
dc.creator.none.fl_str_mv Pérez Arques, Carlos
Navarro Mendoza, María Isabel
Murcia Flores, Laura
Navarro, Eusebio
Garre, Victoriano
Nicolás, Francisco Esteban
author Pérez Arques, Carlos
author_facet Pérez Arques, Carlos
Navarro Mendoza, María Isabel
Murcia Flores, Laura
Navarro, Eusebio
Garre, Victoriano
Nicolás, Francisco Esteban
author_role author
author2 Navarro Mendoza, María Isabel
Murcia Flores, Laura
Navarro, Eusebio
Garre, Victoriano
Nicolás, Francisco Esteban
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Epimutations
Mucor circinelloides
RNA interference
topic Epimutations
Mucor circinelloides
RNA interference
description Epimutations in fungal pathogens are emerging as novel phenomena that could explain the fast-developing resistance to antifungal drugs and other stresses. These epimutations are generated by RNA interference (RNAi) mechanisms that transiently silence specific genes to overcome stressful stimuli. The early-diverging fungus Mucor circinelloides exercises a fine control over two interacting RNAi pathways to produce epimutants: the canonical RNAi pathway and a new RNAi degradative pathway. The latter is considered a non-canonical RNAi pathway (NCRIP) because it relies on RNA-dependent RNA polymerases (RdRPs) and a novel ribonuclease III-like named R3B2 to degrade target transcripts. Here in this work, we uncovered the role of NCRIP in regulating virulence processes and transposon movements through key components of the pathway, RdRP1 and R3B2. Mutants in these genes are unable to launch a proper virulence response to macrophage phagocytosis, resulting in a decreased virulence potential. The transcriptomic profile of rdrp1Δ and r3b2Δ mutants revealed a pre-exposure adaptation to the stressful phagosomal environment even when the strains are not confronted by macrophages. These results suggest that NCRIP represses key targets during regular growth and releases its control when a stressful environment challenges the fungus. NCRIP interacts with the RNAi canonical core to protect genome stability by controlling the expression of centromeric retrotransposable elements. In the absence of NCRIP, these retrotransposons are robustly repressed by the canonical RNAi machinery; thus, supporting the antagonistic role of NCRIP in containing the epimutational pathway. Both interacting RNAi pathways might be essential to govern host-pathogen interactions through transient adaptations, contributing to the unique traits of the emerging infection mucormycosis.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10952/7200
url http://hdl.handle.net/10952/7200
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:RIUCAM. Repositorio Institucional de la Universidad Católica San Antonio de Murcia
instname:Universidad Católica San Antonio de Murcia (UCAM)
instname_str Universidad Católica San Antonio de Murcia (UCAM)
reponame_str RIUCAM. Repositorio Institucional de la Universidad Católica San Antonio de Murcia
collection RIUCAM. Repositorio Institucional de la Universidad Católica San Antonio de Murcia
repository.name.fl_str_mv
repository.mail.fl_str_mv
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