Intergenerational transport of double-stranded RNA in <i>C. elegans</i> can limit heritable epigenetic changes.

Shugarts Devanapally, Nathan M; Sathya, Aishwarya; Yi, Andrew L; Chan, Winnie M; Marre, Julia A; Jose, Antony M · Elife · 2025

basic_science · Level V

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Abstract

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 nematode <i>Caenorhabditis elegans</i> silencing 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 the <i><b>s</b>id-1</i>-<b>d</b>ependent <b>g</b>ene <i>sdg-1</i> that last for more than 100 generations after restoration of SID-1. The SDG-1 protein is enriched in perinuclear germ granules required for heritable RNA silencing but is expressed from a retrotransposon targeted by such silencing. This auto-inhibitory loop suggests how retrotransposons could persist by hosting genes that regulate their own silencing.

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