A balance between silencing foreign DNA and protecting self in Caenorhabditis elegans

Unrestrained transposon mobilization threatens genome integrity. To survive, organisms have evolved silencing pathways capable of distinguishing self from non-self. This review emphasizes C. elegans genome defense with a particular emphasis on systems-level detection of foreign DNA and the balance between silencing and protective pathways. Abundant small RNAs (piRNAs and siRNAs), aberrant DNA structures (e.g., introns), and heterochromatin domains largely mediate silencing. For example, CRISPR-based manipulation of endogenous piRNAs has elucidated precise targeting rules and a novel, conserved role in tuning endogenous germline gene expression. Protective pathways are only just becoming clear: small RNA pathways (CSR-1), deamination of endogenous dsRNA, and a pervasive, embedded DNA watermark (PATCs) can all counteract silencing to protect endogenous genes.