Nuclear RNAi in C. elegans: The Hunt for New nrdes

RNA interference is a conserved mode of gene regulation in which small RNAs ‘silence’ the expression of complementary mRNAs. RNAi is best known to regulate mRNA stability and translation in the cytoplasm. However, RNAi can also act in the nucleus at the level of transcription. Our lab studies nuclear RNAi in the nematode C. elegans. We have previously identified four genes required for nuclear RNAi; we call these the nuclear RNAi defectives (nrdes). The NRDEs localize to the nucleus where they associate with nascent transcripts and inhibit RNA Polymerase II transcription elongation. The exact mechanism by which the NRDEs regulate transcription remains unclear. In order to address this issue of mechanism, I conducted a forward genetic screen to identify additional nrde factors. Here I will describe two new nrdes, nrde-7 and nrde-8, and their putative roles in nuclear RNAi.