Model of the role of piRNAs in the distinction between self and nonself RNAs in the worm C. elegans. In germlines, a piRNA complex associated with PRG-1 inspects RNAs to identify targets with imperfect complementarity. A system based on the use of protein CSR-1 and endo-siRNA protects cellular mRNAs (1a). Recognition of the target, a transposable element or a foreign element by a piRNA (1b) recruits an RNA-dependent RNA polymerase (RdRP) (2). This enzyme generates many small RNA guides called 22G-RNA (3) which bind WAGO9, either to amplify the signal by recruiting RdRP and generating new 22G-RNA, or to inactivate the transposon. There are two mechanisms of repression that operate, in the nucleus by epigenetic modifications (4a) and in the cytoplasm by degradation of the target (4b).