PERIOD-controlled deadenylation of the <i>timeless</i> transcript in the <i>Drosophila</i> circadian clock.

Abstract

The <i>Drosophila</i> circadian oscillator relies on a negative transcriptional feedback loop, in which the PERIOD (PER) and TIMELESS (TIM) proteins repress the expression of their own gene by inhibiting the activity of the CLOCK (CLK) and CYCLE (CYC) transcription factors. A series of posttranslational modifications contribute to the oscillations of the PER and TIM proteins but few posttranscriptional mechanisms have been described that affect mRNA stability. Here we report that down-regulation of the POP2 deadenylase, a key component of the CCR4-NOT deadenylation complex, alters behavioral rhythms. Down-regulating POP2 specifically increases TIM protein and <i>tim</i> mRNA but not <i>tim</i> pre-mRNA, supporting a posttranscriptional role. Indeed, reduced POP2 levels induce a lengthening of <i>tim</i> mRNA poly(A) tail. Surprisingly, such effects are lost in <i>per</i>^<i>0</i> mutants, supporting a PER-dependent inhibition of <i>tim</i> mRNA deadenylation by POP2. We report a deadenylation mechanism that controls the oscillations of a core clock gene transcript.