Intergenerational transport of double-stranded RNA limits heritable epigenetic changes

RNAs in circulation carry sequence-specific regulatory information between cells in plant, animal, and host-pathogen systems. Such RNA can cross generational boundaries, as evidenced by somatic double-stranded RNA (dsRNA) in the nematodeC. eleganssilencing genes of matching sequence in progeny. Here we dissect the intergenerational path taken by dsRNA from parental circulation and discover that cytosolic import through the dsRNA importer SID-1 in the parental germline and/or developing progeny varies with developmental time and dsRNA substrates. Loss of SID-1 enhances initiation of heritable RNA silencing within the germline and causes changes in the expression of thesid-1-dependentgenesdg-1that last for more than 100 generations after restoration of SID-1. The SDG-1 protein is enriched in perinuclear Z granules required for heritable RNA silencing but is expressed from a retrotransposon targeted by such silencing. This auto-inhibitory loop reveals how retrotransposons could persist by hosting genes that regulate their own silencing.