Insulin post-transcriptional regulation via PARP12-mediated ADP-ribosylation
ADP-ribosylation is a common modification that occurs in proteins and nucleic acids, regulating many cellular processes ranging from DNA repair to inflammatory signaling. ADP-ribosylation plays an important role in cancer biology, infectious diseases, and obesity, but its role in the development of type 1 diabetes (T1D) is not well understood. Here, we studied the role of ADP-ribosyltransferase PARP12 in T1D development. PARP12 expression is highly induced in human islets treated with pro-inflammatory cytokines or ß cells from diabetic donors. Proteomics analysis of MIN6 insulin-producing cells identified that the RNA machinery is regulated by PARP12 during inflammation. PARP12 also ADP-ribosylates 150 mRNAs, including the insulin mRNA. This mRNA ADP-ribosylation in turn modifies transcript localization and halts translation. Overall, our data identified a role for PARP12 in ADP-ribosylation and translation halting of mRNAs, which may affect insulin production during insulitis. Overall design: We have No Cytokine cocktail Nontarget siRNA and PARP12 siRNA treated group and Cytokine cocktail Nontarget siRNA and PARP12 siRNA treated groups (4 groups total). Each of those groups is split to be treated with Control and AF1521 beads making a total 8 groups. Each group have 4 biological replicates.