EBAX-1/ZSWIM8 destabilizes miRNAs, resulting in transgenerational inheritance of a predatory trait
Shiela Pearl Quiobe, Ata Kalirad, Waltraud Röseler, Hanh Witte, Yinan Wang, Christian Rödelsperger, Ralf J. Sommer
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.