Suppression of PERIOD protein abundance and circadian cycling by the Drosophila clock mutation timeless.

The timeless mutation (tim) leads to loss of circadian behavioral rhythms in Drosophila melanogaster. The effects of tim on rhythmicity involve interactions with period (per), a second essential clock gene, as the tim mutation suppresses circadian oscillations of per transcription and blocks nuclear localization of a PER reporter protein. In the present study it was found that the tim mutant constitutively produces a low level of PER protein that is comparable with that produced late in the day by wild-type flies. In addition, it was shown that tim suppresses circadian cycling of PER protein abundance and circadian regulation of PER phosphorylation. Transfer of wild-type flies to constant light also suppressed cycling of PER abundance and phosphorylation and produced constitutively low levels of PER. In the tim mutant there was no additional effect of constant light on PER. These results suggest that constant light and the tim mutation produce related changes in the underlying biological clock. We further suggest that the multiple effects of tim are due to a primary effect on per expression at the posttranscriptional level. The effects of tim on behavioral rhythms and per RNA cycling are therefore likely to involve effects on PER protein through previously proposed feedback mechanisms.