However, our data do not discriminate between direct and indirect effects of Fingolimod Nocturnin on the iNOS message, and it is possible that Nocturnin is destabilizing some other message that encodes an iNOS destabilizer. However, the recent observation that many RNAs can exist in stable, but short-tailed forms suggests that the role of deadenylation may be more complex than previously thought. Nevertheless, we have shown that Nocturnin does not localize to known RNA storage compartments such as stress granules or P-bodies, and is not present in polysomes. Also, loss of Nocturnin in MEFs results in loss of both iNOS mRNA and iNOS protein, suggesting that Nocturnin does not simply convert the iNOS message into a stable short-tailed but translationally silent form. It is possible that Nocturnin competes with other more robust deadenylases for certain target mRNAs. In in vitro assays, Nocturnin has a less robust activity than other deadenylases such as PARN, although there are many caveats in interpreting such assays with generic substrates and isolated enzymes. Perhaps a “slow” or inefficient deadenylase protects messages from rapid deadenylation and subsequent decay. Repeated attempts to measure the poly tail lengths of the iNOS mRNA in our Noc KO cells were unsuccessful due to the extremely low levels of iNOS message. But support for such an idea comes from analysis of the CCR4 family members in humans where the “yeast-like” members with the extended leucine-rich N-terminal domains have robust deadenylase activity while the other members, including Nocturnin, do not. One of the members of this latter class, Ccr4d, was shown to participate in a deadenylation complex in nuclear Cajal bodies. Perhaps Nocturnin has diverged to take on a role that stabilizes mRNAs, either through its deadenylase activity or some other unknown activity. Recent reports have shown that the circadian clock modulates the innate immune system in physiologically important ways. Both the clock and the immune system are under significant post-transcriptional control although the inflammatory system has been much more extensively studied in this regard. Many mRNAs that encode inflammatory response proteins have short half-lives and this instability is necessary to avoid accumulation of potentially harmful protein products in times when they are not needed. Our data strongly suggest that Nocturnin plays an important role in stabilization of the hepatic iNOS message both following LPS stimulation and during the night within the circadian cycle. Why are the basal levels of iNOS mRNA rhythmic in the liver? Perhaps this is related to a circadian change in susceptibility to inflammatory signals. It has been reported that mice exhibit significantly higher lethality to LPS and TNFa administration during their resting phase and that this rhythm is under circadian control. Our demonstration that mice lacking Nocturnin exhibit higher survivability following LPS injection suggests that Nocturnin is playing a role in this daily change in sensitivity. Whether this resistance to LPS is due to the changes we observe on iNOS stability is not yet known and further studies will be required to more carefully examine other aspects of the innate immune response in the Noc KO mice.