Defective mitochondrial mRNA maturation is associated with spastic ataxia

Am J Hum Genet. 2010 Nov 12;87(5):655-60. doi: 10.1016/j.ajhg.2010.09.013. Epub 2010 Oct 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Cerebellar Ataxia / genetics*
  • Child
  • Child, Preschool
  • DNA-Directed RNA Polymerases / genetics*
  • Female
  • Genes, Mitochondrial*
  • Humans
  • Male
  • Mitochondrial Proteins / genetics*
  • Molecular Sequence Data
  • Mutation
  • Optic Atrophy / genetics
  • Paraparesis, Spastic / genetics*
  • Pedigree
  • RNA, Messenger*
  • RNA, Mitochondrial


  • Mitochondrial Proteins
  • RNA, Messenger
  • RNA, Mitochondrial
  • mitochondrial messenger RNA
  • DNA-Directed RNA Polymerases
  • MTPAP protein, human