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PTBP1 Positively Regulates the Translation of Circadian Clock Gene, Period1

Wanil Kim1, Jae-Cheon Shin2, Kyung-Ha Lee1

  • 1Division of Cosmetic Science and Technology, Daegu Haany University, Hanuidae-ro 1, Gyeongsan, Gyeongbuk 38610, Korea.

International Journal of Molecular Sciences
|September 24, 2020
PubMed

Insights

Polypyrimidine tract-binding protein 1 (PTBP1) regulates the translation of the core circadian clock gene Period1 (Per1) via its 5'-untranslated region. PTBP1 is crucial for rhythmic Per1 protein expression and fine-tuning the circadian system.

Area of Science:

  • Molecular Biology
  • Chronobiology
  • Gene Regulation

Background:

  • Circadian rhythms are governed by core clock genes exhibiting diurnal oscillations.
  • Period1 (Per1) is a key gene in the negative-feedback loop of the circadian clock.
  • Translational regulation plays a significant role in circadian clock gene expression.

Purpose of the Study:

  • To investigate the posttranscriptional and translational regulation of the mouse Per1 gene.
  • To identify the role of the 5"-untranslated region (5"-UTR) in Per1 translation.
  • To elucidate the function of polypyrimidine tract-binding protein 1 (PTBP1) in Per1 regulation.

Main Methods:

  • Analysis of the Per1 5 ahydro-UTR for internal ribosomal entry site (IRES) activity.
  • Investigation of PTBP1 binding to the Per1 5 ahydro-UTR.
  • Assessment of PTBP1's effect on Per1 mRNA and protein levels and oscillation.

Main Results:

  • The Per1 5 ahydro-UTR contains an IRES that promotes translation.
  • PTBP1 binds to the Per1 5 ahydro-UTR and enhances IRES-mediated translation.
  • Reduced PTBP1 levels decrease PER1 protein but not mRNA, affecting expression amplitude but not phase.
  • PTBP1 influences the mRNA amplitudes of other clock genes like Cryptochrome 1 (Cry1) and Per3.

Conclusions:

  • PTBP1 is essential for the rhythmic translation of Per1.
  • PTBP1 fine-tunes the overall circadian system by regulating Per1 expression.
  • The findings highlight the importance of translational control in circadian rhythmicity.

Keywords:
IRESPTBP1Per1circadian rhythm

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