PERIOD-controlled deadenylation of the timeless transcript in the Drosophila circadian clock

Proc Natl Acad Sci U S A. 2019 Mar 19;116(12):5721-5726. doi: 10.1073/pnas.1814418116. Epub 2019 Mar 4.


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.

Keywords: CAF1/POP2; CCR4–NOT complex; circadian rhythms; clock genes; mRNA poly(A) tail.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / genetics
  • Animals
  • CLOCK Proteins / genetics
  • Circadian Clocks / genetics
  • Circadian Clocks / physiology*
  • Circadian Rhythm / physiology
  • Down-Regulation
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / genetics
  • Gene Expression Regulation
  • Period Circadian Proteins / metabolism
  • Period Circadian Proteins / physiology*
  • Phosphorylation
  • RNA, Messenger / metabolism
  • Ribonucleases
  • Transcription, Genetic


  • ARNTL Transcription Factors
  • Drosophila Proteins
  • PER protein, Drosophila
  • Period Circadian Proteins
  • RNA, Messenger
  • tim protein, Drosophila
  • CLOCK Proteins
  • CCR4 protein, Drosophila
  • Ribonucleases