The Circadian Deadenylase Nocturnin Is Necessary for Stabilization of the iNOS mRNA in Mice

dc.contributor.authorNiu, Shuangen
dc.contributor.authorShingle, Danielle L.en
dc.contributor.authorGarbarino-Pico, Eduardoen
dc.contributor.authorKojima, Shihokoen
dc.contributor.authorGilbert, Mistyen
dc.contributor.authorGreen, Carla B.en
dc.contributor.departmentBiological Sciencesen
dc.date.accessioned2018-07-26T19:10:34Zen
dc.date.available2018-07-26T19:10:34Zen
dc.date.issued2011-11-02en
dc.description.abstractNocturnin 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 (t1/2 = 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.en
dc.description.sponsorshipNational Institutes of Healthen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0026954en
dc.identifier.issue11en
dc.identifier.urihttp://hdl.handle.net/10919/84411en
dc.identifier.urlhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0026954en
dc.identifier.volume6en
dc.language.isoen_USen
dc.publisherPLoSen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleThe Circadian Deadenylase Nocturnin Is Necessary for Stabilization of the iNOS mRNA in Miceen
dc.title.serialPLoS Oneen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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