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.

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