Molecular model of OPMD.

<p>The first molecular defect in OPMD would be a general decrease in the cleavage/polyadenylation reaction resulting from affected PABPN1 function. This would not lead to a reduction of mRNA levels at steady-state for most mRNAs, but would lead to such a decrease for mRNAs actively deadenylated by Smg/CCR4-NOT, among which mRNAs involved in mitochondrial function. This would result in mitochondrial dysfunction and in turn affected muscle function. Additional mechanisms of mRNA regulation occurring downstream of the first defect in cleavage/polyadenylation are also expected to be involved. CPSF, Cleavage and polyadenylation specificity factor; CstF, Cleavage stimulation factor; PAP, poly(A) polymerase.</p>