Endogenous siRNAs play an essential role in silencing non-self DNA elements, such as transposons and repetitive DNA elements that could be harmful for the host genome, but they are also important in fine-tuning gene expression of protein coding genes. In this issue, Sam Gu and colleagues use genome engineering in the C. elegans germline to dissect the mechanisms of differential regulation of self and non-self siRNAs. They insert fragments of somatic and germline genes into the Cer3 retrotransposon, which is a hotspot for siRNA production, and find that the germline siRNAs are suppressed compared with flanking Cer3 siRNAs and somatic siRNAs. By mutating oma-1, a germline gene that they inserted in the Cer3 locus, they discover that siRNA suppression is local and dependent on the presence of a homologous DNA sequence in the target gene. The authors go on to determine that suppression is dependent on the presence of complementary mRNA. Interestingly, siRNA suppression is not dependent on the Argonaute proteins HRDE-1 or CSR-1, but is dependent on P-granule components, indicating that siRNA biogenesis and suppression could be localised to these structures. Together, these data indicate that siRNA turnover is a key regulatory mechanism for controlling unwanted gene silencing.
