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.

Andrew H Crosby ¹, 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

Affiliations

Affiliation

1 Centre for Medical Genetics, St. George's University London, UK. acrosby@sgul.ac.uk

PMID: 20970105 DOI: 10.1016/j.ajhg.2010.09.013

Abstract

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.

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