Identification of an active RNAi pathway in Candida albicans

• 成果类型: Article
• 署名作者: Iracane, Elise; Arias-Sarda, Cristina; Maufrais, Corinne; V. Ene, Iuliana; d'Enfert, Christophe; Buscaino, Alessia
• 署名单位: University of Kent; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; INRAE
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12120
• DOI: 10.1073/pnas.2315926121
• 发表日期: 2024-04-23
• 关键词: antifungal drug-resistance; crystal-structure; fungal pathogen; in-vitro; slicer; gene; argonaute2; EVOLUTION; interference; infections

摘要

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 Saccharomyces cerevisiae , have lost the RNAi pathway. Until now evidence has been lacking for a fully functional RNAi pathway in Candida albicans , a human fungal pathogen considered critically important by the World Health Organization. Here, we demonstrated that the widely used C. albicans reference strain (SC5314) contains an inactivating missense mutation in the gene encoding for the central RNAi component Argonaute. In contrast, most other C. albicans 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 C. albicans RNAi machinery represses expression of subtelomeric gene families. Thus, an intact and functional RNAi pathway exists in C. albicans , highlighting the importance of using multiple reference strains when studying this dangerous pathogen.