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The Evolutionary Significance of RNAi in the Fungal Kingdom
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Article

The RNAi Mechanism Regulates a New Exonuclease Gene Involved in the Virulence of Mucorales

Departmento de Genética y Microbiología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, Spain
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Authors to whom correspondence should be addressed.
Academic Editor: Raffaella Maria Balestrini
Int. J. Mol. Sci. 2021, 22(5), 2282; https://doi.org/10.3390/ijms22052282
Received: 13 January 2021 / Revised: 16 February 2021 / Accepted: 22 February 2021 / Published: 25 February 2021
(This article belongs to the Special Issue Functional and Mechanistic Diversity of RNA Silencing in Fungi)
Mucormycosis is a lethal disease caused by Mucorales, which are emerging as human causes that explain the high mortality for this disease. Consequently, the research community is searching for virulence determinants that could be repurposed as targets to develop new treatments against mucormycosis. Our work explores an RNA interference (RNAi)-based approach to find targets involved in the virulence of Mucorales. A transcriptomewide analysis compared sRNAs and their target mRNAs in two Mucor lusitanicus different pathotypes, virulent and avirulent, generating a list of 75 loci selected by their differential sRNA accumulation in these strains. As a proof of concept and validity, an experimental approach characterized two loci showing opposite behavior, confirming that RNAi activity causes their differential expression in the two pathotypes. We generated deletion mutants for two loci and a knockin-strain overexpressing for one of these loci. Their functional analysis in murine virulence assays identified the gene wex1, a putative DEDDy exonuclease with RNase domains, as an essential factor for virulence. The identification of wex1 showed the potential of our approach to discover virulence factors not only in Mucorales but also in any other fungal model with an active RNAi machinery. More importantly, it adds a new layer to the biological processes controlled by RNAi in M. lusitanicus, confirming that the Dicer-dependent RNAi pathway can silence gene expression to promote virulence. View Full-Text
Keywords: mucormycosis; Mucor lusitanicus; Mucorales; RNAi; exonuclease; wex1 gene; virulence; virulence factor mucormycosis; Mucor lusitanicus; Mucorales; RNAi; exonuclease; wex1 gene; virulence; virulence factor
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MDPI and ACS Style

Pérez-Arques, C.; Navarro-Mendoza, M.I.; Murcia, L.; Navarro, E.; Garre, V.; Nicolás, F.E. The RNAi Mechanism Regulates a New Exonuclease Gene Involved in the Virulence of Mucorales. Int. J. Mol. Sci. 2021, 22, 2282. https://doi.org/10.3390/ijms22052282

AMA Style

Pérez-Arques C, Navarro-Mendoza MI, Murcia L, Navarro E, Garre V, Nicolás FE. The RNAi Mechanism Regulates a New Exonuclease Gene Involved in the Virulence of Mucorales. International Journal of Molecular Sciences. 2021; 22(5):2282. https://doi.org/10.3390/ijms22052282

Chicago/Turabian Style

Pérez-Arques, Carlos, María I. Navarro-Mendoza, Laura Murcia, Eusebio Navarro, Victoriano Garre, and Francisco E. Nicolás 2021. "The RNAi Mechanism Regulates a New Exonuclease Gene Involved in the Virulence of Mucorales" International Journal of Molecular Sciences 22, no. 5: 2282. https://doi.org/10.3390/ijms22052282

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