Evidence for a central role of transcription in the timing mechanism of a circadian clock.
The retinal circadian clock in the isolated in vitro eye of the marine mollusc Bulla gouldiana exhibits a phase-dependent requirement for transcription. The transcription-sensitive phase extends through most of the subjective day and therefore is substantially longer than the previously reported translation-sensitive phase. Lower concentrations of transcription inhibitors yield a significant dose-dependent lengthening of circadian period. Clock motion can be stopped by a high concentration of the transcription inhibitor 5,6-dichlorobenz-imidazole riboside (DRB) when applied during the sensitive phase; after withdrawal of the inhibitor, motion resumes from the phase at which it was stopped. In a double-pulse experiment, phase shifts to light pulses applied after DRB pulses, and not during the translation-sensitive phase, indicate that the inhibition of transcription has immediate effects on the phase of the clock. These data suggest that DRB-induced phase shifts are independent of translation, which implies that the rate of transcription itself plays a significant role in the mechanism underlying the generation of the circadian cycle.
Khalsa
S B
SB
Department of Biology, University of Virginia, Charlottesville 22903, USA.
Whitmore
D
D
Bogart
B
B
Block
G D
GD
D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D003839:Deoxyadenosines / Q000494:pharmacology; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D008974:Mollusca / Q000502:physiology*; D014176:Protein Biosynthesis / Q000187:drug effects; D011687:Purines / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D003839:Deoxyadenosines; D011687:Purines; C016588:6-methylpurine; D004004:Dichlororibofuranosylbenzimidazole; D003513:Cycloheximide; C058120:cordycepin