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

Abstract

The mouse PERIOD1 (mPER1) protein, along with other clock proteins, plays a crucial role in the maintenance of circadian rhythm. 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 is 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 interaction 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.