Fig_9.tif (268.28 kB)
Molecular model of OPMD.
figure
posted on 2015-03-27, 04:22 authored by Aymeric Chartier, Pierre Klein, Stéphanie Pierson, Nicolas Barbezier, Teresa Gidaro, François Casas, Steven Carberry, Paul Dowling, Laurie Maynadier, Maëlle Bellec, Martine Oloko, Claude Jardel, Bodo Moritz, George Dickson, Vincent Mouly, Kay Ohlendieck, Gillian Butler-Browne, Capucine Trollet, Martine SimoneligThe 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.
