Role of the Non-Canonical RNAi Pathway in the Antifungal Resistance and Virulence of Mucorales
Mucorales are the causal agents for the lethal disease known as mucormycosis. Mortality rates of mucormycosis can reach up to 90%, due to the mucoralean antifungal drug resistance and the lack of effective therapies. A concerning urgency among the medical and scientific community claims to find targ...
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doaj-7bc44e2fcc554a8a8db10282f26d82332021-04-17T23:00:50ZengMDPI AGGenes2073-44252021-04-011258658610.3390/genes12040586Role of the Non-Canonical RNAi Pathway in the Antifungal Resistance and Virulence of MucoralesJosé Tomás Cánovas-Márquez0María Isabel Navarro-Mendoza1Carlos Pérez-Arques2Carlos Lax3Ghizlane Tahiri4José Antonio Pérez-Ruiz5Damaris Lorenzo-Gutiérrez6Silvia Calo7Sergio López-García8Eusebio Navarro9Francisco Esteban Nicolás10Victoriano Garre11Laura Murcia12Departamento de Genética y Microbiología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, SpainDepartment of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USADepartment of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USADepartamento de Genética y Microbiología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, SpainDepartamento de Genética y Microbiología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, SpainDepartamento de Genética y Microbiología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, SpainDepartamento de Genética y Microbiología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, SpainSchool of Natural and Exact Sciences, Pontificia Universidad Católica Madre y Maestra, Santiago de los Caballeros 51033, Dominican RepublicDepartamento de Genética y Microbiología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, SpainDepartamento de Genética y Microbiología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, SpainDepartamento de Genética y Microbiología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, SpainDepartamento de Genética y Microbiología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, SpainDepartamento de Genética y Microbiología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, SpainMucorales are the causal agents for the lethal disease known as mucormycosis. Mortality rates of mucormycosis can reach up to 90%, due to the mucoralean antifungal drug resistance and the lack of effective therapies. A concerning urgency among the medical and scientific community claims to find targets for the development of new treatments. Here, we reviewed different studies describing the role and machinery of a novel non-canonical RNAi pathway (NCRIP) only conserved in Mucorales. Its non-canonical features are the independence of Dicer and Argonaute proteins. Conversely, NCRIP relies on RNA-dependent RNA Polymerases (RdRP) and an atypical ribonuclease III (RNase III). NCRIP regulates the expression of mRNAs by degrading them in a specific manner. Its mechanism binds dsRNA but only cuts ssRNA. NCRIP exhibits a diversity of functional roles. It represses the epimutational pathway and the lack of NCRIP increases the generation of drug resistant strains. NCRIP also regulates the control of retrotransposons expression, playing an essential role in genome stability. Finally, NCRIP regulates the response during phagocytosis, affecting the multifactorial process of virulence. These critical NCRIP roles in virulence and antifungal drug resistance, along with its exclusive presence in Mucorales, mark this pathway as a promising target to fight against mucormycosis.https://www.mdpi.com/2073-4425/12/4/586virulenceantifungal resistancenon-canonical RNAiepimutantR3B2RdRP |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
José Tomás Cánovas-Márquez María Isabel Navarro-Mendoza Carlos Pérez-Arques Carlos Lax Ghizlane Tahiri José Antonio Pérez-Ruiz Damaris Lorenzo-Gutiérrez Silvia Calo Sergio López-García Eusebio Navarro Francisco Esteban Nicolás Victoriano Garre Laura Murcia |
spellingShingle |
José Tomás Cánovas-Márquez María Isabel Navarro-Mendoza Carlos Pérez-Arques Carlos Lax Ghizlane Tahiri José Antonio Pérez-Ruiz Damaris Lorenzo-Gutiérrez Silvia Calo Sergio López-García Eusebio Navarro Francisco Esteban Nicolás Victoriano Garre Laura Murcia Role of the Non-Canonical RNAi Pathway in the Antifungal Resistance and Virulence of Mucorales Genes virulence antifungal resistance non-canonical RNAi epimutant R3B2 RdRP |
author_facet |
José Tomás Cánovas-Márquez María Isabel Navarro-Mendoza Carlos Pérez-Arques Carlos Lax Ghizlane Tahiri José Antonio Pérez-Ruiz Damaris Lorenzo-Gutiérrez Silvia Calo Sergio López-García Eusebio Navarro Francisco Esteban Nicolás Victoriano Garre Laura Murcia |
author_sort |
José Tomás Cánovas-Márquez |
title |
Role of the Non-Canonical RNAi Pathway in the Antifungal Resistance and Virulence of Mucorales |
title_short |
Role of the Non-Canonical RNAi Pathway in the Antifungal Resistance and Virulence of Mucorales |
title_full |
Role of the Non-Canonical RNAi Pathway in the Antifungal Resistance and Virulence of Mucorales |
title_fullStr |
Role of the Non-Canonical RNAi Pathway in the Antifungal Resistance and Virulence of Mucorales |
title_full_unstemmed |
Role of the Non-Canonical RNAi Pathway in the Antifungal Resistance and Virulence of Mucorales |
title_sort |
role of the non-canonical rnai pathway in the antifungal resistance and virulence of mucorales |
publisher |
MDPI AG |
series |
Genes |
issn |
2073-4425 |
publishDate |
2021-04-01 |
description |
Mucorales are the causal agents for the lethal disease known as mucormycosis. Mortality rates of mucormycosis can reach up to 90%, due to the mucoralean antifungal drug resistance and the lack of effective therapies. A concerning urgency among the medical and scientific community claims to find targets for the development of new treatments. Here, we reviewed different studies describing the role and machinery of a novel non-canonical RNAi pathway (NCRIP) only conserved in Mucorales. Its non-canonical features are the independence of Dicer and Argonaute proteins. Conversely, NCRIP relies on RNA-dependent RNA Polymerases (RdRP) and an atypical ribonuclease III (RNase III). NCRIP regulates the expression of mRNAs by degrading them in a specific manner. Its mechanism binds dsRNA but only cuts ssRNA. NCRIP exhibits a diversity of functional roles. It represses the epimutational pathway and the lack of NCRIP increases the generation of drug resistant strains. NCRIP also regulates the control of retrotransposons expression, playing an essential role in genome stability. Finally, NCRIP regulates the response during phagocytosis, affecting the multifactorial process of virulence. These critical NCRIP roles in virulence and antifungal drug resistance, along with its exclusive presence in Mucorales, mark this pathway as a promising target to fight against mucormycosis. |
topic |
virulence antifungal resistance non-canonical RNAi epimutant R3B2 RdRP |
url |
https://www.mdpi.com/2073-4425/12/4/586 |
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