Figure 2.
The misregulated alternative splicing and misregulated alternative polyadenylation model in human DM1. CUGexp mRNAs sequester muscleblind-like (MBNL) and activate the expression of CUGBP Elav-Like Family Member 1 (CELF1) to a steady-state level through protein kinase C (PKC)-mediated hyperphosphorylation. These changes cause spliceopathy and fetal splicing shifts in adult tissues. In addition, CELF1 binding to 3′ UTRs leads to mRNA repression and decay while MBNL binding to 3′ UTRs promotes mRNA stabilization, localization to membrane compartments, and translation.