原创力文档the circadian deadenylase nocturnin is necessary for stabilization of the inos mrna in mice生理deadenylase nocturnin对于伊诺mrna的稳定是必要的老鼠.pdfVIP
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the circadian deadenylase nocturnin is necessary for stabilization of the inos mrna in mice生理deadenylase nocturnin对于伊诺mrna的稳定是必要的老鼠
The Circadian Deadenylase Nocturnin Is Necessary for
Stabilization of the iNOS mRNA in Mice
Shuang Niu1.¤a, Danielle L. Shingle1,2., Eduardo Garbarino-Pico1¤b, Shihoko Kojima1,2, Misty Gilbert 1¤c,
Carla B. Green1,2*
1 Department of Biology, University of Virginia, Charlottesville, Virginia, United States of America, 2 Department of Neuroscience, University of Texas Southwestern
Medical Center, Dallas, Texas, United States of America
Abstract
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 TNFa and iNOS mRNAs during the first three hours following LPS treatment, but by 24 hours,
while TNFa 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 TNFa
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.
Citation: Niu S, Shingle DL, Garbarino-Pico E, Kojima S, Gilbert M, et al. (2011) The Circadian Deadenylase Nocturnin Is Necessary for Stabili
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