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

doi:10.1016/j.ajhg.2010.09.013

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 journal › Article › peer-review

71 Citations (Scopus)

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.

Original language	English
Pages (from-to)	655-60
Number of pages	6
Journal	American Journal of Human Genetics
Volume	87
Issue number	5
DOIs	https://doi.org/10.1016/j.ajhg.2010.09.013
Publication status	Published - 12 Nov 2010

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Crosby, A. H., Patel, H., Chioza, B. A., Proukakis, C., Gurtz, K., Patton, M. A., Sharifi, R., Harlalka, G., Simpson, M. A., Dick, K., Reed, J. A., Al-Memar, A., Chrzanowska-Lightowlers, Z. M. A., Cross, H. E., & Lightowlers, R. N. (2010). Defective mitochondrial mRNA maturation is associated with spastic ataxia. American Journal of Human Genetics, 87(5), 655-60. https://doi.org/10.1016/j.ajhg.2010.09.013

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title = "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.",

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

year = "2010",

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doi = "10.1016/j.ajhg.2010.09.013",

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Crosby, AH, Patel, H , Chioza, BA, Proukakis, C, Gurtz, K, Patton, MA, Sharifi, R, Harlalka, G, Simpson, MA, Dick, K, Reed, JA, Al-Memar, A, Chrzanowska-Lightowlers, ZMA, Cross, HE & Lightowlers, RN 2010, 'Defective mitochondrial mRNA maturation is associated with spastic ataxia', American Journal of Human Genetics, vol. 87, no. 5, pp. 655-60. https://doi.org/10.1016/j.ajhg.2010.09.013

TY - JOUR

T1 - Defective mitochondrial mRNA maturation is associated with spastic ataxia

AU - Crosby, Andrew H

AU - Patel, Heema

AU - Chioza, Barry A

AU - Proukakis, Christos

AU - Gurtz, Kay

AU - Patton, Michael A

AU - Sharifi, Reza

AU - Harlalka, Gaurav

AU - Simpson, Michael A

AU - Dick, Katherine

AU - Reed, Johanna A

AU - Al-Memar, Ali

AU - Chrzanowska-Lightowlers, Zofia M A

AU - Cross, Harold E

AU - Lightowlers, Robert N

PY - 2010/11/12

Y1 - 2010/11/12

N2 - 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.

AB - 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.

U2 - 10.1016/j.ajhg.2010.09.013

DO - 10.1016/j.ajhg.2010.09.013

M3 - Article

C2 - 20970105

SN - 1537-6605

VL - 87

SP - 655

EP - 660

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 5

ER -

Defective mitochondrial mRNA maturation is associated with spastic ataxia

Abstract

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