The Potential Regulation of L1 Mobility by RNA Interference

The hypothesis that RNA interference constrains L1 mobility seemsinherently reasonable: L1 mobility can be dangerous and L1 RNA,the presumed target of RNAi, serves as a criticalretrotransposition intermediate. Despite its plausibility, prooffor this hypothesis has been difficult to obtain. Studiesattempting to link the L1 retrotransposition frequency toalterations in RNAi activity have been hampered by the long timesrequired to measure retrotransposition frequency, the pleiotropicand toxic effects of altering RNAi over similar time periods, andthe possibility that other cellular machinery may contribute tothe regulation of L1s. Another problem is that the commonly usedL1 reporter cassette may serve as a substrate for RNAi. Here wereview the L1-RNAi hypothesis and describe a genetic assay with amodified reporter cassette that detects approximately 4 times moreL1 insertions than the conventional retrotransposition assay