The Role of PTB in Insulin mRNA Stability Control

Rickard      G. Fred; Linda      Tillmar; Nils      Welsh

Abstract

Although extensively studied, there are still many unanswered questions regarding the regulation of insulin gene expression. This is important to further investigate since it will help us understand the pathophysiology of some types of diabetes. The insulin mRNA has a long half-life and changes in insulin mRNA stability, induced by glucose, are likely to be regulated through specific mechanisms. Recent findings indicate that the polypyrimidine tract binding protein (PTB), also named hnRNP I, by binding to the 3-UTR (untranslated region) of the insulin mRNA molecule, stabilizes the messenger thereby participating in the glucose-induced increase in insulin mRNA. This review will focus on recent findings pertinent to PTB subcellular localization and function. It appears that PTB shuttles between the nucleus and the cytosol, and that protein kinase A (PKA)-mediated PTB phosphorylation promotes PTB translocation to the cytosol, an event that might enhance insulin mRNA stability. We will also review beta-cell signaling events that may control the mRNA stabilizing effect of PTB.

Keywords: PTB, hnRNP I, mRNA stability, Insulin gene expression, Diabetes