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Rhythmic interaction between Period1 mRNA and hnRNP Q leads to circadian time-dependent translation

Kyung-Ha Lee1, Kyung-Chul Woo, Do-Yeon Kim

  • 1Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea.

Molecular and Cellular Biology
|November 30, 2011
PubMed

Insights

The circadian expression of the mouse PERIOD1 (mPER1) protein is controlled by rhythmic translation of its mRNA, influenced by an internal ribosomal entry site (IRES) and mhnRNP Q. This reveals posttranscriptional regulation of core clock genes.

Area of Science:

  • Molecular Biology
  • Chronobiology
  • Genetics

Background:

  • The mouse PERIOD1 (mPER1) protein is vital for circadian rhythms and links the circadian and cell cycle systems.
  • Understanding the regulation of mPER1 is key to comprehending circadian rhythm maintenance.

Purpose of the Study:

  • To investigate the regulatory mechanisms governing the circadian expression of mPER1.
  • To elucidate the role of translational control and posttranscriptional modifications in circadian rhythmicity.

Main Methods:

  • Analysis of mPer1 mRNA and protein expression levels.
  • Investigating the function of the 5' untranslated region (5'-UTR) and internal ribosomal entry site (IRES) in mPer1 translation.
  • Knockdown experiments of the trans-acting factor mouse heterogeneous nuclear ribonucleoprotein Q (mhnRNP Q).

Main Results:

  • Circadian expression of mPER1 is regulated by both transcriptional modulation and rhythmic translational control of mPer1 mRNA.
  • An IRES element in the 5'-UTR of mPer1 mRNA, along with mhnRNP Q, controls time-dependent translation.
  • mhnRNP Q knockdown reduced mPER1 levels and delayed its expression without affecting mRNA levels.
  • IRES-mediated translation rate shows phase-dependent characteristics due to rhythmic mPer1 mRNA and mhnRNP Q interactions.

Conclusions:

  • Demonstrated 5'-UTR-mediated rhythmic mPer1 translation.
  • Provided evidence for posttranscriptional regulation of circadian rhythmicity in core clock genes.
  • Highlighted the role of mhnRNP Q and IRES in controlling circadian gene expression at the translational level.

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