Defective Mitochondrial mRNA Maturation Is Associated with Spastic Ataxia

In human mitochondria, polyadenylation of mRNA undertaken by the nuclear encoded mitochondrial poly(A) RNA polymerase, is essential for maintaining mitochondrial gene expression Our molecular investigation of an autosomal recessive spastic ataxia with optic atrophy, present among the Old Order Amish, identified a mutation of MTPAP associated with the disease phenotype When subjected to poly(A) tail length assays mitochondrial mRNAs from affected individuals were shown to have severely truncated poly(A) tails Although defective mitochondrial DNA maintenance underlies a well described group of clinical disorders, our findings reveal a defect of mitochondrial mRNA maturation associated with human disease and imply that this disease mechanism should be considered in other complex neurodegenerative disorders