Regulation of gene expression by alternative polyadenylation and mRNA instability in hyperglycaemic mesangial cells

We have used mRNA differential display to identify a novel high-glucose-reg ulated gene (HGRG-14) in human mesangial cells cultured for up to 21 days i n 30 mM D-glucose. The mRNA of HGRG-14 seems to be regulated post-transcrip tionally and encodes a small polypeptide of molecular mass 13 kDa. The nati ve protein occurs as a dimer. The recombinant protein is a substrate for ca sein kinase II kinase, At high glucose concentrations, HGRG-14 protein leve ls decrease. This correlates with the appearance of a long form of HGRG-14 mRNA under high-glucose conditions. This form has a long 3' untranslated re gion containing several ATTTA RNA-destabilizing sequences and has a short h alf-life. A truncated, more stable mRNA that lacks the long 3' untranslated region is produced at 4 mM D-glucose. The switch from the truncated to the long-form transcript is detected within 2 h of exposure to 30 mM D-glucose , indicating that hyperglycaemic conditions have an acute effect on HGRG-14 mRNA processing.