Understanding a central miRNA/RNAi factor: mammalian Dicer. Genetic data in C. elegans indicates that Dicer depletion results in loss of RNAi and developmental defects. In S. pombe, knockout of Dicer results in loss of heterochromatic silencing, suggesting a potential role for small RNAs in transcriptional gene silencing. Dicer depletion has been shown to reduce the processing of small RNAs, indicating that Dicer may be the enzyme for producing small regulatory RNAs. To test the role of Dicer in mammals, and in collaboration with Brian Harfe, we have created cell lines and mice that are conditional for the gene knockout of Dicer. These will be useful reagents for examining the role of Dicer in RNAi and development.

Our current lab focus relates to the post-transcriptional regulation of gene expression as mitigated through small RNAs. We believe that the small regulatory RNAs that we have discovered are just the ‘tip of the iceberg’ in a set of biologies that we are far from understanding.