UCSF

The ability to distinguish self from non-self nucleic acids enables eukaryotes to suppress mobile elements and maintain genome integrity. In organisms from protist to human, this function is performed by RNA silencing pathways. There have been major advances in our understanding of the RNA silencing machinery, but the mechanisms by which these pathways distinguish self from non-self remain unclear. Recent studies in the yeast C. neoformans indicate that transposon-derived transcripts encode suboptimal introns and tend to stall in spliceosomes, which promotes the biogenesis of siRNA that targets these transcripts. These findings identify gene expression signal strength as a metric by which a foreign element can be distinguished from a host gene, and reveal a new function for introns and the spliceosome in genome defense. Anticipating that these principles may apply to RNA silencing in other systems, we discuss strong hints in the literature suggesting that the spliceosome may guide small RNA biogenesis in the siRNA and piRNA pathways of plants and animals.