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Abstract
The mouse PERIOD1 (mPER1) protein, along with other clock proteins, plays a crucial role in the maintenance of circadian rhythms. mPER1 also provides an important link between the circadian system and the cell cycle system. Here we show that the circadian expression of mPER1 is regulated by rhythmic translational control of mPer1 mRNA together with transcriptional modulation. This time-dependent translation was controlled by an internal ribosomal entry site (IRES) element in the 5′ untranslated region (5′-UTR) of mPer1 mRNA along with the trans-acting factor mouse heterogeneous nuclear ribonucleoprotein Q (mhnRNP Q). Knockdown of mhnRNP Q caused a decrease in mPER1 levels and a slight delay in mPER1 expression without changing mRNA levels. The rate of IRES-mediated translation exhibits phase-dependent characteristics through rhythmic interactions between mPer1 mRNA and mhnRNP Q. Here, we demonstrate 5′-UTR-mediated rhythmic mPer1 translation and provide evidence for posttranscriptional regulation of the circadian rhythmicity of core clock genes.
SUPPLEMENTAL MATERIAL
Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.06177-11.
ACKNOWLEDGMENTS
We thank Choogon Lee for kindly providing anti-PER1 antibody, K. Mikoshiba for the anti-SYNCRIP-N antibody, and Kyungjin Kim and Jiwon Lee for the Per2-dsLuc plasmid.
This work was supported by grants from the National Research Foundation of Korea (20100030089, 20100002146, and 20100019706), the Brain Korea 21 program, the World Class University program (R31-10105), and the Regional Core Research Program/Anti-aging and Well-being Research Center, funded by the Korean Ministry of Education, Science, and Technology.