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Updated: Jan 28, 2026

Circadian Entrainment of Drosophila Melanogaster
Published on: June 3, 2020
PERIOD-controlled deadenylation of the timeless transcript in the Drosophila circadian clock
Brigitte Grima1, Christian Papin1, Béatrice Martin1
1Institut des Neurosciences Paris-Saclay, Université Paris-Sud, Université Paris-Saclay, CNRS, 91190 Gif-sur-Yvette, France.
Insights
Down-regulating POP2, a key deadenylase, disrupts circadian rhythms by lengthening the TIMELESS (TIM) mRNA poly(A) tail. This effect is dependent on the PERIOD (PER) protein, revealing a novel posttranscriptional regulatory mechanism in the Drosophila clock.
Area of Science:
- Chronobiology
- Molecular Biology
- Genetics
Background:
- The Drosophila circadian clock utilizes a transcriptional feedback loop involving PERIOD (PER) and TIMELESS (TIM) proteins.
- Posttranslational modifications are known regulators, but posttranscriptional mechanisms affecting mRNA stability are less understood.
Purpose of the Study:
- To investigate the role of the POP2 deadenylase in regulating circadian rhythms at the posttranscriptional level.
- To elucidate the mechanism by which POP2 influences the stability of core clock gene transcripts.
Main Methods:
- Genetic manipulation of POP2 levels in Drosophila.
- Analysis of TIM protein and mRNA expression, including pre-mRNA and poly(A) tail length.
- Assessment of behavioral rhythms and analysis in PER mutant backgrounds.
Main Results:
- Down-regulation of POP2 leads to altered behavioral rhythms.
- POP2 reduction specifically increases TIM protein and mRNA levels, not pre-mRNA, indicating posttranscriptional regulation.
- Reduced POP2 lengthens the poly(A) tail of TIM mRNA, a mechanism dependent on PER.
Conclusions:
- POP2, a component of the CCR4-NOT deadenylation complex, plays a crucial role in regulating circadian rhythms.
- A novel PER-dependent mechanism involving POP2 controls TIM mRNA deadenylation and stability.
- This study identifies a key posttranscriptional regulatory mechanism governing circadian clock gene expression.
Abstract:
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 per 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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