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Nucleic Acids Research Advance Access published online on November 14, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn893
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© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

RNA

Mouse period 2 mRNA circadian oscillation is modulated by PTB–mediated rhythmic mRNA degradation

Kyung-Chul Woo1, Tae-Don Kim1,2, Kyung-Ha Lee1, Do-Yeon Kim1, Wanil Kim1, Kyung-Yeol Lee3 and Kyong-Tai Kim1,*

1Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, 2Center for stem cell research, Korea Research Institute of Bioscience and Biotechnology, 111, Gwahangno, Yuseong-gu, Daejeon and 3School of Dentistry, Chonbuk National University, Jeonju, South Korea

*To whom correspondence should be addressed. Tel: +82 54 279 2297; Fax: +82 54 279 2199; Email: ktk{at}postech.ac.kr

Received May 14, 2008. Revised October 12, 2008. Accepted October 25, 2008.

Circadian mRNA oscillations are the main feature of core clock genes. Among them, period 2 is a key component in negative-feedback regulation, showing robust diurnal oscillations. Moreover, period 2 has been found to have a physiological role in the cell cycle or the tumor suppression. The present study reports that 3'-untranslated region (UTR)-dependent mRNA decay is involved in the regulation of circadian oscillation of period 2 mRNA. Within the mper2 3'UTR, both the CU-rich region and polypyrimidine tract-binding protein (PTB) are more responsible for mRNA stability and degradation kinetics than are other factors. Depletion of PTB with RNAi results in mper2 mRNA stabilization. During the circadian oscillations of mper2, cytoplasmic PTB showed a reciprocal expression profile compared with mper2 mRNA and its peak amplitude was increased when PTB was depleted. This report on the regulation of mper2 proposes that post-transcriptional mRNA decay mediated by PTB is a fine-tuned regulatory mechanism that includes dampening-down effects during circadian mRNA oscillations.


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