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

Publication ,  Journal Article
Pérez-Arques, C; Navarro-Mendoza, MI; Murcia, L; Navarro, E; Garre, V; Nicolás, FE
Published in: International journal of molecular sciences
February 2021

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.

Duke Scholars

Published In

International journal of molecular sciences

DOI

EISSN

1422-0067

ISSN

1422-0067

Publication Date

February 2021

Volume

22

Issue

5

Start / End Page

2282

Related Subject Headings

  • Virulence
  • Transcriptome
  • RNA, Fungal
  • RNA Interference
  • Mutation
  • Mucorales
  • Genes, Fungal
  • Gene Expression Regulation, Fungal
  • Exonucleases
  • Chemical Physics
 

Citation

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MLA
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Pérez-Arques, C., Navarro-Mendoza, M. I., Murcia, L., Navarro, E., Garre, V., & Nicolás, F. E. (2021). The RNAi Mechanism Regulates a New Exonuclease Gene Involved in the Virulence of Mucorales. International Journal of Molecular Sciences, 22(5), 2282. https://doi.org/10.3390/ijms22052282
Pérez-Arques, Carlos, María Isabel Navarro-Mendoza, Laura Murcia, Eusebio Navarro, Victoriano Garre, and Francisco Esteban Nicolás. “The RNAi Mechanism Regulates a New Exonuclease Gene Involved in the Virulence of Mucorales.International Journal of Molecular Sciences 22, no. 5 (February 2021): 2282. https://doi.org/10.3390/ijms22052282.
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 Feb;22(5):2282.
Pérez-Arques, Carlos, et al. “The RNAi Mechanism Regulates a New Exonuclease Gene Involved in the Virulence of Mucorales.International Journal of Molecular Sciences, vol. 22, no. 5, Feb. 2021, p. 2282. Epmc, doi:10.3390/ijms22052282.
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 Feb;22(5):2282.

Published In

International journal of molecular sciences

DOI

EISSN

1422-0067

ISSN

1422-0067

Publication Date

February 2021

Volume

22

Issue

5

Start / End Page

2282

Related Subject Headings

  • Virulence
  • Transcriptome
  • RNA, Fungal
  • RNA Interference
  • Mutation
  • Mucorales
  • Genes, Fungal
  • Gene Expression Regulation, Fungal
  • Exonucleases
  • Chemical Physics