RNA interference (RNAi) is a powerful technique for gene silencing but the mechanisms by which double-stranded RNA (dsRNA) affects target gene activity is still poorly understood. In the Early Edition of the Proceedings of the National Academy of Sciences, Nathaniel Dudley and colleagues from the University of North Carolina at Chapel Hill describe a method for isolating dsRNA molecules that prevent RNAi and give insights into the mechanisms involved.

Dudley et al. co-injected pools of dsRNAs into Caenorhabditiselegans embryos and screened for inhibition of RNAi-induced embryonic lethality. This led them to isolate gfl-1, a homolog of the human GAS41 gene, a predicted DNA-binding protein identified by virtue of its amplification in glioblastomas. The authors used their 'RNAi-to-RNAi' assay to test polycomb-group genes and found that polycomb-like genes mes-3, mes-4 and mes-6 were also required for RNAi. Furthermore, mutants null for these genes were also RNAi-deficient (Proc Natl Acad Sci USA 2002, 10.1073/pnas.062605199).

Further work will be required to understand the role of these chromatin-binding factors in the mechanisms of RNAi.