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

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 <i>Pristionchus pacificus</i>, 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. <i>Ppa-ebax-1</i> mutants are transgenerational inheritance defective, and <i>Ppa-</i>EBAX-1 destabilizes the clustered microRNA family <i>miR-2235a/miR-35.</i> Deletions of a cluster of 44 identical <i>miR-2235a</i> 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.