Defective mitochondrial mRNA maturation is associated with spastic ataxia.

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.

• Authors: 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
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 87 Issue 5 Pg. 655-60 (Nov 12 2010) ISSN: 1537-6605 [Electronic] United States
• PMID: 20970105 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Chemical References

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

Topics

• 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