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EBAX-1/ZSWIM8 destabilizes miRNAs resulting in transgenerational inheritance of a predatory trait

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Feb 27, 2025 version files 6 GB

Abstract

Environmental influences on traits and associated transgenerational epigenetic inheritance have widespread implications, but remain controversial and underlying mechanisms poorly understood. We introduce long-term environmental induction experiments on alternative diets in Pristionchus pacificus, a nematode exhibiting mouth-form plasticity including predation, by propagating 110 isogenic lines for 101 generations with associated food-reversal experiments. We found dietary induction and subsequent transgenerational inheritance of the predatory morph and identified a role of ubiquitin ligase EBAX-1/ZSWIM8 in this process. Ppa-ebax-1 mutants are transgenerational inheritance-defective and Ppa-EBAX-1 destabilizes the clustered microRNA family miR-2235a/miR-35. Deletions of a cluster of 44 identical miR-2235a copies resulted in precocious and extended transgenerational inheritance of the predatory morph. These findings indicate that EBAX-1/ZSWIM8 destabilizes miRNAs resulting in transgenerational inheritance, suggesting a role for target-directed miRNA degradation.