Abstract
The hypothesis that RNA interference constrains L1 mobility seems
inherently reasonable: L1 mobility can be dangerous and L1 RNA,
the presumed target of RNAi, serves as a critical
retrotransposition intermediate. Despite its plausibility, proof
for this hypothesis has been difficult to obtain. Studies
attempting to link the L1 retrotransposition frequency to
alterations in RNAi activity have been hampered by the long times
required to measure retrotransposition frequency, the pleiotropic
and toxic effects of altering RNAi over similar time periods, and
the possibility that other cellular machinery may contribute to
the regulation of L1s. Another problem is that the commonly used
L1 reporter cassette may serve as a substrate for RNAi. Here we
review the L1-RNAi hypothesis and describe a genetic assay with a
modified reporter cassette that detects approximately 4 times more
L1 insertions than the conventional retrotransposition assay.