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陕西快乐十分中奖规律:PERIOD-controlled deadenylation of the timeless transcript in the Drosophila circadian clock
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Circadian oscillators rely on transcriptional negative feedback loops. In Drosophila, the key transcriptional repressor PERIOD (PER) slowly accumulates during the night under the control of its partner TIMELESS (TIM). A large number of posttranslational mechanisms regulate PER and TIM stability, but no mechanisms affecting the stability of their transcripts have been described. mRNA stability depends on the length of the poly(A) tail. We show that a deadenylase, POP2, shortens tim mRNA poly(A) tail, thus decreasing tim mRNA and TIM protein levels. Moreover, POP2 activity on tim mRNA appears to be inhibited by PER itself. These results reveal polyadenylation control of a core clock gene transcript and suggest that the repressor of the feedback loop also acts as a posttranscriptional regulator.
The Drosophila 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 tim mRNA but not tim pre-mRNA, supporting a posttranscriptional role. Indeed, reduced POP2 levels induce a lengthening of tim mRNA poly(A) tail. Surprisingly, such effects are lost in per0 mutants, supporting a PER-dependent inhibition of tim mRNA deadenylation by POP2. We report a deadenylation mechanism that controls the oscillations of a core clock gene transcript.
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Author contributions: B.G., E.J., and F.R. designed research; B.G., C.P., B.M., E.C., P.P., and E.J. performed research; B.G., C.P., B.M., E.C., P.P., E.J., and F.R. analyzed data; and B.G. and F.R. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1814418116/-/DCSupplemental.
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