Defective mitochondrial mrna maturation is associated with spastic ataxia

Andrew H. Crosby, Heema Patel, Barry A. Chioza, Christos Proukakis, Kay Gurtz, Michael A. Patton, Reza Sharifi, Gaurav Harlalka, Michael A. Simpson, Katherine Dick, Johanna A. Reed, Ali Al-Memar, Zofia M.A. Chrzanowska-Lightowlers, Harold E. Cross, Robert N. Lightowlers

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)655-660
Number of pages6
JournalAmerican Journal of Human Genetics
Issue number5
StatePublished - Nov 12 2010

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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