Transcriptome changes caused by loss of WAGO-4 is remembered in wild type offspring.

The worm-specific Argonaute WAGO-4 has been shown to be involved in epigenetic memory in C. elegans , however, its mode of action remains unclear. Here, we use a wago-4 deletion mutant to show that general changes to 22G-RNAs, the small RNA cofactor binding WAGO-4 , do not correlate with changes to mRNA levels. We also show that the function of WAGO-4 differs in L4 larvae and in adult worms, and, importantly, we show that mRNA misregulation caused by loss of WAGO-4 persists in wild-type offspring of deletion mutants for at least five generations.