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Identification of an active RNAi pathway in Candida albicans

Iracane, Elise, Arias-Sardá, Cristina, Maufrais, Corinne, Ene, Iuliana V, d'Enfert, Christophe, Buscaino, Alessia (2024) Identification of an active RNAi pathway in Candida albicans. Proceedings of the National Academy of Sciences of the United States of America, 121 (17). Article Number e231592612. ISSN 0027-8424. E-ISSN 1091-6490. (doi:10.1073/pnas.2315926121) (KAR id:105784)

Abstract

RNA interference (RNAi) is a fundamental regulatory pathway with a wide range of functions, including regulation of gene expression and maintenance of genome stability. Although RNAi is widespread in the fungal kingdom, well-known species, such as the model yeast , have lost the RNAi pathway. Until now evidence has been lacking for a fully functional RNAi pathway in , a human fungal pathogen considered critically important by the World Health Organization. Here, we demonstrated that the widely used reference strain (SC5314) contains an inactivating missense mutation in the gene encoding for the central RNAi component Argonaute. In contrast, most other isolates contain a canonical Argonaute protein predicted to be functional and RNAi-active. Indeed, using high-throughput small and long RNA sequencing combined with seamless CRISPR/Cas9-based gene editing, we demonstrate that an active RNAi machinery represses expression of subtelomeric gene families. Thus, an intact and functional RNAi pathway exists in , highlighting the importance of using multiple reference strains when studying this dangerous pathogen.

Item Type: Article
DOI/Identification number: 10.1073/pnas.2315926121
Additional information: For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Uncontrolled keywords: gene editing; candida albicans - genetics; RNA interference; subtelomeres; fungal pathogens; humans; Saccharomyces cerevisiae - metabolism; Genomic Instability
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Biosciences
Funders: Biotechnology and Biological Sciences Research Council (https://ror.org/00cwqg982)
Leverhulme Trust (https://ror.org/012mzw131)
Agence Nationale de la Recherche (https://ror.org/00rbzpz17)
SWORD Depositor: JISC Publications Router
Depositing User: JISC Publications Router
Date Deposited: 03 May 2024 13:36 UTC
Last Modified: 05 Nov 2024 13:11 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/105784 (The current URI for this page, for reference purposes)

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