Immediate early response of the circadian polyA ribonuclease nocturnin to two extracellular stimuli

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Abstract
Nocturnin (Noc, also called Ccrn4l [carbon catabolite repression 4-like]) is a circadian deadenylase that is rhythmically expressed in multiple tissues in mice with peak mRNA levels in early night. Since several other circadian genes are induced by extracellular stimuli, we tested the hypothesis that Noc is acutely regulated in NIH3T3 cells. A serum shock and the phorbol ester TPA induced Noc transcript levels in quiescent NIH3T3 cultures while dexamethasone and forskolin, which are known to induce other clock genes in culture, were without effect. NOC protein levels also were induced by serum. The half-life of the TPA-induced Noc mRNA is short, and the inhibition of protein synthesis by cycloheximide prevents Noc mRNA degradation and revealed a 30-fold increase in the transcript levels after 4 h of TPA treatment. Since this acute induction is not dependent on protein synthesis, Noc behaves like other immediate early genes. Remarkably, these acute effects are specific to Noc as the mRNAs encoding other known mouse deadenylases, CCR4, CAF1, PAN2, and PARN, were not induced in the same paradigm. Our data show that in addition to its robust circadian regulation, Noc expression can be regulated acutely, and imply that it can respond directly and specifically to physiological cues. NOC may act in turning off the expression of genes that are required to be silenced as a response to these extracellular signals.