PTBP1 Positively Regulates the Translation of Circadian Clock Gene,Period1

Abstract

Circadian oscillations of mRNAs and proteins are the main features of circadian clock genes. Among them,Period1(Per1) is a key component in negative-feedback regulation, which shows a robust diurnal oscillation and the importance of circadian rhythm and translational regulation of circadian clock genes has been recognized. In the present study, we investigated the 5 '-untranslated region (5 '-UTR) of the mouse core clock gene,Per1, at the posttranscriptional level, particularly its translational regulation. The 5 '-UTR ofPer1was found to promote its translation via an internal ribosomal entry site (IRES). We found that polypyrimidine tract-binding protein 1 (PTBP1) binds to the 5 '-UTR ofPer1and positively regulates the IRES-mediated translation ofPer1without affecting the levels ofPer1mRNA. The reduction of PTBP1 level also decreased the endogenous levels of the PER1 protein but not of its mRNA. As for the oscillation of PER1 expression, the disruption of PTBP1 levels lowered the PER1 expression but not the phase of the oscillation. PTBP1 also changed the amplitudes of the mRNAs of other circadian clock genes, such asCryptochrome 1(Cry1) andPer3. Our results suggest that the PTBP1 is important for rhythmic translation ofPer1and it fine-tunes the overall circadian system.