The timing of lin-4 RNA accumulation controls the timing of postembryonic developmental events in Caenorhabditis elegans

The lin-4 gene encodes a small RNA that is required to translationally repr ess lin-14 toward the end of the first larval stage of Caenorhabditis elega ns development. To determine if the timing of LIN-14 protein down-regulatio n depends on the temporal profile of lin-4 RNA level, we analyzed the stage -specificity of lin-4 RNA expression during wild-type development and exami ned the phenotypes of transgenic worms that overexpress lin-4 RNA during th e first larval stage. We found that lin-4 RNA first becomes detectable at a pproximately 12 h of wild-type larval development and rapidly accumulates t o nearly maximum levels by 16 h. This profile of lin-4 RNA accumulation cor responded to the timing of LIN-14 protein down-regulation. Transgenic strai ns that express elevated levels of lin-4 RNA prior to 12 h of development d isplay reduced levels of LIN-14 protein and precocious phenotypes consisten t with abnormally early loss of lin-14 activity. These results indicate tha t the temporal profile of lin-4 RNA accumulation specifies the timing of LI N-14 down-regulation and thereby controls the timing of postembryonic devel opmental events. (C) 1999 Academic Press.