SignificanceIdiopathic inflammatory bowel disease (IBD) is associated with the gut microbiota and immune system of the host; however, the precise pathogenesis of IBD is poorly defined. We show that specific deletion of the endoribonuclease Regnase-1 in intestinal epithelial cells relieves the symptoms of experimental colitis during acute inflammation. Regnase-1 deficiency potentiates mTOR signaling and purine metabolism in the colon epithelium. These data provide insight into the role of epithelial Regnase-1 in IBD.

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An increase of nucleolar number and size has made nucleoli essential markers for cytology and tumour development. However, the underlying basis for their structural integrity and abundance remains unclear. Protein phosphatase PPM1D was found to be up-regulated in different carcinomas including breast cancers. Here, we demonstrate for the first time that PPM1D regulates nucleolar formation via inducing an increased phosphorylation of the nucleolar protein NPM. We show that PPM1D overexpression induces an increase in the nucleolar number regardless of p53 status. We also demonstrated that specific sequential phosphorylation of NPM is important for nucleolar formation and that PPM1D is a novel upstream regulator of this phosphorylation pathway. These results enhance our understanding of the molecular mechanisms that govern nucleoli formation by demonstrating that PPM1D regulates nucleolar formation by regulating NPM phosphorylation status through a novel signalling pathway, PPM1D-CDC25C-CDK1-PLK1.