G.P.9 02 Long expansion and deletion of the polyalanine domain in PABPN1 lead to a modified aggregation pattern

Abstract

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset disease caused by (GCN)n triplet expansions in the polyalanine domain coding sequence of the poly(A)-binding protein nuclear 1 (PABPN1). The pathology is characterized by the formation of filamentous intranuclear inclusions (INI) in the nucleus of skeletal muscle fibers. PABPN1 is an ubiquitous polyadenylation factor essential for the lengthening of poly(A) tails on every mRNA. The INIs observed in OPMD are rich in PABPN1, components of ubiquitin–proteasome pathway, molecular chaperones, poly(A)mRNA, and sequester other mRNA-processing factors.