We use the nematode worm Caenorhabditis elegans as a model organism in which to study the role of PIWI Argonaute (AGO) and other AGO pathways. Recently we have shown that worm PIWI AGOs use their piRNA cofactors to constantly scan the germline for foreign mRNA sequences. There are tens of thousands of distinct piRNA species expressed in the germline, and PIWI AGOs can target while allowing a few mismatches between the piRNA guide and the mRNA target sequence. Thus, given their large numbers and sequence diversity, dozens of piRNAs will recognize and base-pair partially to any foreign mRNA sequences expressed in the germline.
Once a foreign mRNA is identified, the PIWI AGO recruits an RNA-dependent RNA polymerase (RdRP) to initiate the amplification of "memory" small RNAs that precisely match the foreign sequences. These memory small RNAs are loaded onto silencing AGOs that not only silence the foreign mRNA but are also transmitted to progeny in both the egg and the sperm, allowing progeny to maintain silencing. This mode of inheritance is not mediated by the DNA but by direct transmission of AGO/small-RNA complexes. Thus animals with exactly the same DNA content can transmit different patterns of gene expression to their offspring.
