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

NIU S; SHINGLE DL; GARBARINO PICO E; KOJIMA S; GILBERT M; GREEN CB

PUBLIC LIBRARY SCIENCE

Año: 2011 vol. 6 p. 26954 - 26954

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, mic