Nocturnin is a member of the CCR4 deadenylase family, and its expression is 
under circadian control with peak levels at night. Because it can remove poly(A) 
tails from mRNAs, it is presumed to play a role in post-transcriptional control 
of circadian gene expression, but its target mRNAs are not known. Here we 
demonstrate that Nocturnin expression is acutely induced by the endotoxin 
lipopolysaccharide (LPS). Mouse embryo fibroblasts (MEFs) lacking Nocturnin 
exhibit normal patterns of acute induction of TNFα and iNOS mRNAs during the 
first three hours following LPS treatment, but by 24 hours, while TNFα mRNA 
levels are indistinguishable from WT cells, iNOS message is significantly 
reduced 20-fold. Accordingly, analysis of the stability of the mRNAs showed that 
loss of Nocturnin causes a significant decrease in the half-life of the iNOS 
mRNA (t(1/2) = 3.3 hours in Nocturnin knockout MEFs vs. 12.4 hours in wild type 
MEFs), while having no effect on the TNFα message. Furthermore, mice lacking 
Nocturnin lose the normal nighttime peak of hepatic iNOS mRNA, and have improved 
survival following LPS injection. These data suggest that Nocturnin has a novel 
stabilizing activity that plays an important role in the circadian response to 
inflammatory signals.