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.
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.
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.
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.
Abstract
Mucormycosis is a lethal disease caused by Mucorales, which are emerging as human pathogens with virulent behavior. Antifungal resistance and ineffective treatments are two major 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 transcriptome-wide 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 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. But, 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.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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