Small interfering RNA mediates gene regulation in the nucleus of Caenorhabditis elegans

Noncoding RNAs (ncRNAs) are widely present in higher eukaryotes and involved in a range of biological processes to regulate gene expression, genome integrity, and development. Growing evidence has emerged that ncRNAs are also involved in the generation of diseases. Small regulatory RNAs have shown potential as disease marker, drug targets, and therapeutic drugs. Our research is focused on the molecular mechanism and biological roles of small interfering RNA (siRNA)-regulated gene expression in metazoans. By conducting genetic screenings in the model organism C. elegans, a novel nuclear RNAi defective (Nrde) pathway and the critical players have been identified through which siRNA performs gene silencing in the nucleus. This work not only demonstrated that nuclear RNAi machinery exists in metazoans, but also led to several discoveries. For example, we found that small RNAs are sorted between distinct subcellular compartments by associating with particular Argonaute proteins. siRNAs regulate transcription elongation by inhibiting RNA polymerase Ⅱ and elicit premature termination. Furthermore, it was found that this pathway is necessary for the transgenerational maintenance of acquired RNAi.