Mechanisms of epigenetic regulation by C. elegans nuclear RNA interference pathways

RNA interference (RNAi) is a highly conserved gene regulatory phenomenon whereby Argonaute/small RNA (AGO/sRNA) complexes target transcripts by antisense complementarity to modulate gene expression. While initially appreciated as a cytoplasmic process, RNAi can also occur in the nucleus where AGO/sRNA complexes are recruited to nascent transcripts. Nuclear AGO/sRNA complexes recruit co-factors that regulate transcription by inhibiting RNA Polymerase II, modifying histones, compacting chromatin and, in some organisms, methylating DNA. C. elegans has a longstanding history in unveiling the mechanisms of RNAi and has become an outstanding model to delineate the mechanisms underlying nuclear RNAi. In this review we highlight recent discoveries in the field of nuclear RNAi in C. elegans and the roles of nuclear RNAi in the regulation of gene expression, chromatin organization, genome stability, and transgenerational epigenetic inheritance.