ArticlePLoS genetics2017
A non-canonical RNA degradation pathway suppresses RNAi-dependent epimutations in the human fungal pathogen Mucor circinelloides.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 72 citations in OpenAlex.
- Molecular Mechanisms, Diagnosis, and Therapeutic Strategies of Antifungal Resistance in Filamentous Fungi.Journal of fungi (Basel, Switzerland) · 2026Review
- Aneuploidy promotes transient stress adaptation and metabolic flexibility in the human fungal pathogen Aspergillus fumigatus.Current biology : CB · 2026Article
- Variable ectopic heterochromatin islands provide an alternative route to antifungal heteroresistance inbioRxiv : the preprint server for biology · 2026Article
- Epimutations driven by RNAi or heterochromatin evoke transient antimicrobial drug resistance in pathogenic Mucor fungi.PLoS biology · 2026Article
- Epimutations driven by RNAi or heterochromatin evoke transient antimicrobial drug resistance in fungi.bioRxiv : the preprint server for biology · 2025Article
- Whole-chromosome duplications drive antimicrobial resistance inbioRxiv : the preprint server for biology · 2025Article
- RNAi epimutations conferring antifungal drug resistance are inheritable.Nature communications · 2025Article
- Celebrating the fifth edition of the International Symposium on Fungal Stress - ISFUS, a decade after its 2014 debut.Fungal biology · 2025Article
- The Dual PathogenJournal of fungi (Basel, Switzerland) · 2025Review
- Direct Targeted Degradation of Transposon RNAs by the Non-Canonical RNAi Pathway of the FungusInternational journal of molecular sciences · 2025Article
- Article
- Symmetric and asymmetric DNA N6-adenine methylation regulates different biological responses in Mucorales.Nature communications · 2024Article
- Challenges and Opportunities Arising from Host-International journal of molecular sciences · 2024Review
- Article
- Molecular mechanisms that govern infection and antifungal resistance in Mucorales.Microbiology and molecular biology reviews : MMBR · 2024Review
- Disruption of theRNA (New York, N.Y.) · 2023Article
- Review
- Heterochromatin and RNAi act independently to ensure genome stability in Mucorales human fungal pathogens.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Molecular mechanisms governing antifungal drug resistance.npj antimicrobials and resistance · 2023Review
- Molecular mechanisms of transgenerational epigenetic inheritance.Nature reviews. Genetics · 2022Review
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Mucorales are a group of basal fungi that includes the casual agents of the human emerging disease mucormycosis. Recent studies revealed that these pathogens activate an RNAi-based pathway to rapidly generate drug-resistant epimutant strains when exposed to stressful compounds such as the antifungal drug FK506. To elucidate the molecular mechanism of this epimutation pathway, we performed a genetic analysis in Mucor circinelloides that revealed an inhibitory role for the non-canonical RdRP-dependent Dicer-independent silencing pathway, which is an RNAi-based mechanism involved in mRNA degradation that was recently identified. Thus, mutations that specifically block the mRNA degradation pathway, such as those in the genes r3b2 and rdrp3, enhance the production of drug resistant epimutants, similar to the phenotype previously described for mutation of the gene rdrp1. Our genetic analysis also revealed two new specific components of the epimutation pathway related to the quelling induced protein (qip) and a Sad-3-like helicase (rnhA), as mutations in these genes prevented formation of drug-resistant epimutants. Remarkably, drug-resistant epimutant production was notably increased in M. circinelloides f. circinelloides isolates from humans or other animal hosts. The host-pathogen interaction could be a stressful environment in which the phenotypic plasticity provided by the epimutant pathway might provide an advantage for these strains. These results evoke a model whereby balanced regulation of two different RNAi pathways is determined by the activation of the RNAi-dependent epimutant pathway under stress conditions, or its repression when the regular maintenance of the mRNA degradation pathway operates under non-stress conditions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.