The circadian deadenylase nocturnin is necessary for stabilization of the iNOS mRNA in mice

Shuang Niu, Danielle L. Shingle, Eduardo Garbarino-Pico, Shihoko Kojima, Misty Gilbert, Carla B. Green

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 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.

Original languageEnglish (US)
Article numbere26954
JournalPLoS One
Volume6
Issue number11
DOIs
StatePublished - Nov 2 2011

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Stabilization
lipopolysaccharides
fibroblasts
Messenger RNA
embryo (animal)
mice
Fibroblasts
Lipopolysaccharides
Embryonic Structures
endotoxins
messenger RNA
half life
injection
RNA Stability
gene expression
liver
nocturnin
Knockout Mice
Endotoxins
Half-Life

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

The circadian deadenylase nocturnin is necessary for stabilization of the iNOS mRNA in mice. / Niu, Shuang; Shingle, Danielle L.; Garbarino-Pico, Eduardo; Kojima, Shihoko; Gilbert, Misty; Green, Carla B.

In: PLoS One, Vol. 6, No. 11, e26954, 02.11.2011.

Research output: Contribution to journalArticle

Niu, Shuang ; Shingle, Danielle L. ; Garbarino-Pico, Eduardo ; Kojima, Shihoko ; Gilbert, Misty ; Green, Carla B. / The circadian deadenylase nocturnin is necessary for stabilization of the iNOS mRNA in mice. In: PLoS One. 2011 ; Vol. 6, No. 11.
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