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A mutation in PNPT1, encoding mitochondrial-RNA-import protein PNPase, causes hereditary hearing loss.

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A mutation in PNPT1, encoding mitochondrial-RNA-import protein PNPase, causes hereditary hearing loss. / von Ameln, Simon; Wang, Geng; Boulouiz, Redouane; Rutherford, Mark A; Smith, Geoffrey M; Li, Yun; Pogoda, Hans-Martin; Nürnberg, Gudrun; Stiller, Barbara; Volk, Alexander; Borck, Guntram; Hong, Jason S; Goodyear, Richard J; Abidi, Omar; Nürnberg, Peter; Hofmann, Kay; Richardson, Guy P; Hammerschmidt, Matthias; Moser, Tobias; Wollnik, Bernd; Koehler, Carla M; Teitell, Michael A; Barakat, Abdelhamid; Kubisch, Christian.

In: AM J HUM GENET, Vol. 91, No. 5, 5, 2012, p. 919-927.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

von Ameln, S, Wang, G, Boulouiz, R, Rutherford, MA, Smith, GM, Li, Y, Pogoda, H-M, Nürnberg, G, Stiller, B, Volk, A, Borck, G, Hong, JS, Goodyear, RJ, Abidi, O, Nürnberg, P, Hofmann, K, Richardson, GP, Hammerschmidt, M, Moser, T, Wollnik, B, Koehler, CM, Teitell, MA, Barakat, A & Kubisch, C 2012, 'A mutation in PNPT1, encoding mitochondrial-RNA-import protein PNPase, causes hereditary hearing loss.', AM J HUM GENET, vol. 91, no. 5, 5, pp. 919-927. <http://www.ncbi.nlm.nih.gov/pubmed/23084290?dopt=Citation>

APA

von Ameln, S., Wang, G., Boulouiz, R., Rutherford, M. A., Smith, G. M., Li, Y., Pogoda, H-M., Nürnberg, G., Stiller, B., Volk, A., Borck, G., Hong, J. S., Goodyear, R. J., Abidi, O., Nürnberg, P., Hofmann, K., Richardson, G. P., Hammerschmidt, M., Moser, T., ... Kubisch, C. (2012). A mutation in PNPT1, encoding mitochondrial-RNA-import protein PNPase, causes hereditary hearing loss. AM J HUM GENET, 91(5), 919-927. [5]. http://www.ncbi.nlm.nih.gov/pubmed/23084290?dopt=Citation

Vancouver

von Ameln S, Wang G, Boulouiz R, Rutherford MA, Smith GM, Li Y et al. A mutation in PNPT1, encoding mitochondrial-RNA-import protein PNPase, causes hereditary hearing loss. AM J HUM GENET. 2012;91(5):919-927. 5.

Bibtex

@article{eae222c65b9346c1a2a1cbe6838b6055,
title = "A mutation in PNPT1, encoding mitochondrial-RNA-import protein PNPase, causes hereditary hearing loss.",
abstract = "A subset of nuclear-encoded RNAs has to be imported into mitochondria for the proper replication and transcription of the mitochondrial genome and, hence, for proper mitochondrial function. Polynucleotide phosphorylase (PNPase or PNPT1) is one of the very few components known to be involved in this poorly characterized process in mammals. At the organismal level, however, the effect of PNPase dysfunction and impaired mitochondrial RNA import are unknown. By positional cloning, we identified a homozygous PNPT1 missense mutation (c.1424A>G predicting the protein substitution p.Glu475Gly) of a highly conserved PNPase residue within the second RNase-PH domain in a family affected by autosomal-recessive nonsyndromic hearing impairment. In vitro analyses in bacteria, yeast, and mammalian cells showed that the identified mutation results in a hypofunctional protein leading to disturbed PNPase trimerization and impaired mitochondrial RNA import. Immunohistochemistry revealed strong PNPase staining in the murine cochlea, including the sensory hair cells and the auditory ganglion neurons. In summary, we show that a component of the mitochondrial RNA-import machinery is specifically required for auditory function.",
keywords = "Animals, Humans, Male, Female, Mice, Amino Acid Sequence, Molecular Sequence Data, Base Sequence, Models, Molecular, Gene Expression, Pedigree, Consanguinity, Chromosome Mapping, Protein Conformation, Cell Line, Exons, *Mutation, Cochlea/metabolism/pathology, Exoribonucleases/chemistry/*genetics/metabolism, Hearing Loss, Sensorineural/*genetics/metabolism, RNA/*metabolism, RNA Transport/*genetics, Zebrafish/genetics/metabolism, Animals, Humans, Male, Female, Mice, Amino Acid Sequence, Molecular Sequence Data, Base Sequence, Models, Molecular, Gene Expression, Pedigree, Consanguinity, Chromosome Mapping, Protein Conformation, Cell Line, Exons, *Mutation, Cochlea/metabolism/pathology, Exoribonucleases/chemistry/*genetics/metabolism, Hearing Loss, Sensorineural/*genetics/metabolism, RNA/*metabolism, RNA Transport/*genetics, Zebrafish/genetics/metabolism",
author = "{von Ameln}, Simon and Geng Wang and Redouane Boulouiz and Rutherford, {Mark A} and Smith, {Geoffrey M} and Yun Li and Hans-Martin Pogoda and Gudrun N{\"u}rnberg and Barbara Stiller and Alexander Volk and Guntram Borck and Hong, {Jason S} and Goodyear, {Richard J} and Omar Abidi and Peter N{\"u}rnberg and Kay Hofmann and Richardson, {Guy P} and Matthias Hammerschmidt and Tobias Moser and Bernd Wollnik and Koehler, {Carla M} and Teitell, {Michael A} and Abdelhamid Barakat and Christian Kubisch",
year = "2012",
language = "English",
volume = "91",
pages = "919--927",
journal = "AM J HUM GENET",
issn = "0002-9297",
publisher = "Cell Press",
number = "5",

}

RIS

TY - JOUR

T1 - A mutation in PNPT1, encoding mitochondrial-RNA-import protein PNPase, causes hereditary hearing loss.

AU - von Ameln, Simon

AU - Wang, Geng

AU - Boulouiz, Redouane

AU - Rutherford, Mark A

AU - Smith, Geoffrey M

AU - Li, Yun

AU - Pogoda, Hans-Martin

AU - Nürnberg, Gudrun

AU - Stiller, Barbara

AU - Volk, Alexander

AU - Borck, Guntram

AU - Hong, Jason S

AU - Goodyear, Richard J

AU - Abidi, Omar

AU - Nürnberg, Peter

AU - Hofmann, Kay

AU - Richardson, Guy P

AU - Hammerschmidt, Matthias

AU - Moser, Tobias

AU - Wollnik, Bernd

AU - Koehler, Carla M

AU - Teitell, Michael A

AU - Barakat, Abdelhamid

AU - Kubisch, Christian

PY - 2012

Y1 - 2012

N2 - A subset of nuclear-encoded RNAs has to be imported into mitochondria for the proper replication and transcription of the mitochondrial genome and, hence, for proper mitochondrial function. Polynucleotide phosphorylase (PNPase or PNPT1) is one of the very few components known to be involved in this poorly characterized process in mammals. At the organismal level, however, the effect of PNPase dysfunction and impaired mitochondrial RNA import are unknown. By positional cloning, we identified a homozygous PNPT1 missense mutation (c.1424A>G predicting the protein substitution p.Glu475Gly) of a highly conserved PNPase residue within the second RNase-PH domain in a family affected by autosomal-recessive nonsyndromic hearing impairment. In vitro analyses in bacteria, yeast, and mammalian cells showed that the identified mutation results in a hypofunctional protein leading to disturbed PNPase trimerization and impaired mitochondrial RNA import. Immunohistochemistry revealed strong PNPase staining in the murine cochlea, including the sensory hair cells and the auditory ganglion neurons. In summary, we show that a component of the mitochondrial RNA-import machinery is specifically required for auditory function.

AB - A subset of nuclear-encoded RNAs has to be imported into mitochondria for the proper replication and transcription of the mitochondrial genome and, hence, for proper mitochondrial function. Polynucleotide phosphorylase (PNPase or PNPT1) is one of the very few components known to be involved in this poorly characterized process in mammals. At the organismal level, however, the effect of PNPase dysfunction and impaired mitochondrial RNA import are unknown. By positional cloning, we identified a homozygous PNPT1 missense mutation (c.1424A>G predicting the protein substitution p.Glu475Gly) of a highly conserved PNPase residue within the second RNase-PH domain in a family affected by autosomal-recessive nonsyndromic hearing impairment. In vitro analyses in bacteria, yeast, and mammalian cells showed that the identified mutation results in a hypofunctional protein leading to disturbed PNPase trimerization and impaired mitochondrial RNA import. Immunohistochemistry revealed strong PNPase staining in the murine cochlea, including the sensory hair cells and the auditory ganglion neurons. In summary, we show that a component of the mitochondrial RNA-import machinery is specifically required for auditory function.

KW - Animals

KW - Humans

KW - Male

KW - Female

KW - Mice

KW - Amino Acid Sequence

KW - Molecular Sequence Data

KW - Base Sequence

KW - Models, Molecular

KW - Gene Expression

KW - Pedigree

KW - Consanguinity

KW - Chromosome Mapping

KW - Protein Conformation

KW - Cell Line

KW - Exons

KW - Mutation

KW - Cochlea/metabolism/pathology

KW - Exoribonucleases/chemistry/genetics/metabolism

KW - Hearing Loss, Sensorineural/genetics/metabolism

KW - RNA/metabolism

KW - RNA Transport/genetics

KW - Zebrafish/genetics/metabolism

KW - Animals

KW - Humans

KW - Male

KW - Female

KW - Mice

KW - Amino Acid Sequence

KW - Molecular Sequence Data

KW - Base Sequence

KW - Models, Molecular

KW - Gene Expression

KW - Pedigree

KW - Consanguinity

KW - Chromosome Mapping

KW - Protein Conformation

KW - Cell Line

KW - Exons

KW - Mutation

KW - Cochlea/metabolism/pathology

KW - Exoribonucleases/chemistry/genetics/metabolism

KW - Hearing Loss, Sensorineural/genetics/metabolism

KW - RNA/metabolism

KW - RNA Transport/genetics

KW - Zebrafish/genetics/metabolism

M3 - SCORING: Journal article

VL - 91

SP - 919

EP - 927

JO - AM J HUM GENET

JF - AM J HUM GENET

SN - 0002-9297

IS - 5

M1 - 5

ER -