Fig. 1

piRNA biogenesis in C. elegans. The fork head (FKH) family transcription factors recognize the 8-nt Ruby motif, then the upstream sequence transcription complex (containing PRDE-1, TOFU-4, TOFU-5, and SNPC-4) binds to piRNA gene promoter and recruits TOFU-3 and TBP-1 to transcribe the 21 U-RNA precursors (26-nt single-stranded RNA transcripts). The 21 U-RNA precursors are exported to cytoplasm, 2 nt is removed by TOFU-1 and TOFU-2 at the 5′ end, and the PETISCO complex (containing PID-3, ERH-2, TOFU-6, and IFE-3) and TOFU-7 enhance maturation. The PICS complex refers to TOFU-6, PICS-1, ERH-2, PID-1 and TOST-1. PARN-1 removes 3 nt in the 3′ end and 2′-O-methyl is methylated by HENN-1 to generate the mature 21 U-RNAs (21-nt single-stranded RNA transcripts). The 21 U-RNAs combine with PRG-1 to form RISC to target and degrade transposons or mRNA directly. Additionally, the piRNAs/PRG-1 complex recruits RdRP to produce massive secondary siRNAs (22G-RNAs) by EGO-1. These 22G-RNAs are loaded into the Argonaute protein and cause post-transcriptional silencing by cleaving transposon or mRNA directly or recruiting H3K9me3, HPL-1 and HPL-2 to induce transcriptional silencing. The piRNA/PRG-1 complex can recognize and differentiate self-transcripts from the non-self-component. The 22G-RNAs load into the CSR-1 Argonaute protein, and once 22G-RNAs/CSR-1 recognize the self-transcript, it will protect mRNA from silencing. The balance between self-recognition and non-self-distinguishing determines the outcome of gene expression in worms