EBAX-1/ZSWIM8 destabilizes miRNAs resulting in transgenerational memory 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 inPristionchus 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 memory of the predatory morph and identified a role of ubiquitin ligase EBAX-1/ZSWIM8 in this process.Ppa-ebax-1mutants have no memory andPpa-EBAX-1 destabilizes the clustered microRNA familymiR-2235a/miR-35.Deletions of a cluster of 44 identicalmiR-2235acopies resulted in precocious and extended transgenerational inheritance of the predatory morph. These findings indicate that EBAX-1/ZSWIM8 destabilizes miRNAs resulting in transgenerational memory, suggesting a role for target-directed miRNA degradation.