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Significance Improved understanding of the epitranscriptomic control process will help decipher regulation of global gene expression. Here, we demonstrate that the cell-signaling inositol pyrophosphate 5-InsP7 stabilizes mRNAs that are normally committed to decay pathways by NUDT3-mediated removal of the protective 5′ cap. We demonstrated this effect of 5-InsP7 in vitro using recombinant NUDT3. Then, we applied pharmacological, genetic, and chemical tools to manipulate cellular levels of 5-InsP7 , thereby showing it to enhance mRNA stability in intact cells. We further demonstrate mRNA stabilization is paralleled by increased abundance of P bodies, which are membraneless condensates that sequester mRNAs from the translating pool. Our demonstration that 5-InsP7 regulates mRNA structure and stability, as well as P-body dynamics, illuminates cell-signaling oversight of cellular homeostasis.

InsP 7 is a small-molecule regulator of NUDT3-mediated mRNA decapping and processing-body dynamics

InsP ₇ is a small-molecule regulator of NUDT3-mediated mRNA decapping and processing-body dynamics