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Updated: Jun 9, 2025

Author Spotlight: RNAi Inheritance and ChIP in C. elegans
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Author Spotlight: RNAi Inheritance and ChIP in C. elegans

Published on: May 5, 2023

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RNAi epimutations conferring antifungal drug resistance are inheritable

Carlos Pérez-Arques, María Isabel Navarro-Mendoza, Ziyan Xu

    Biorxiv : the Preprint Server for Biology
    |October 28, 2024
    PubMed

    Insights

    Epigenetic changes conferring antifungal drug resistance are passed down through generations in the fungus Mucor circinelloides. This transgenerational inheritance relies on small RNAs, not DNA sequence, offering new insights into drug resistance and evolution.

    Area of Science:

    • Mycology
    • Epigenetics
    • Antimicrobial Resistance

    Background:

    • Epimutations alter gene expression without changing DNA sequence, influencing traits like drug resistance.
    • The transgenerational inheritance of epigenetic modifications, particularly via RNA interference (RNAi), in fungi remained largely uncharacterized.
    • Understanding epigenetic inheritance is crucial for addressing challenges posed by antimicrobial drug resistance (AMR).

    Purpose of the Study:

    • To investigate whether RNAi-mediated epimutations conferring antifungal drug resistance can be inherited across generations in *Mucor circinelloides*.
    • To determine the inheritance pattern and molecular mechanisms underlying transgenerational epigenetic inheritance of drug resistance.
    • To explore the role of small RNAs (sRNAs) in transmitting epigenetic information.

    Main Methods:

    • Utilized genetic crosses and phenotypic analysis in *Mucor circinelloides* to track antifungal drug resistance inheritance.
    • Employed molecular techniques to analyze small RNA profiles and other epigenetic marks in parent and progeny strains.
    • Investigated the correlation between specific sRNA signatures and the transmission of drug resistance.

    Main Results:

    • Demonstrated that RNAi-mediated antifungal drug resistance is transgenerationally inherited in *Mucor circinelloides*.
    • Established a DNA sequence-independent, non-Mendelian inheritance pattern for this trait.
    • Identified small RNAs (sRNAs) as the sole determinants of inheritance, transmitting resistance independently of other epigenetic modifications.
    • Observed unique sRNA signature patterns that are passed from parent to progeny.

    Conclusions:

    • RNAi epimutations conferring antifungal drug resistance are heritable across generations in *Mucor circinelloides* via small RNAs.
    • Small RNAs serve as a novel mechanism for transmitting epigenetic information, independent of DNA sequence.
    • Findings provide a framework for detecting epimutations in other pathogens and offer potential strategies to combat antimicrobial drug resistance.

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