RNAi in cell nuclei: potential for a new layer of biological regulation and a new strategy for therapeutic discovery

RNA interference is almost always associated with post-transcriptional silencing in the cytoplasm. MicroRNAs (miRNAs) and critical RNAi protein factors like argonaute (AGO) and trinucleotide repeat binding containing 6 protein (TNRC6), however, are also found in cell nuclei, suggesting that nuclear miRNAs may be targets for gene regulation. Designed small duplex RNAs (dsRNAs) can modulate nuclear processes such as transcription and splicing, suggesting that they can also provide leads for therapeutic discovery. The goal of this Perspective is to provide the background on nuclear RNAi necessary to guide discussions on whether nuclear RNAi can play a role in therapeutic development programs.

Automated summary

RNA interference is associated with post-transcriptional silencing in the cytoplasm, but nuclear miRNAs and RNAi protein factors have been found, suggesting the potential of nuclear RNAi in gene regulation and therapeutic development. Designed small duplex RNAs can modulate nuclear processes, providing leads for therapeutic discovery.