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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
A mutation in PNPT1, encoding mitochondrial-RNA-import protein PNPase, causes hereditary hearing loss
American Journal of Human Genetics, Volume 91, No. 5, Year 2012
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Description
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. © 2012 The American Society of Human Genetics.
Authors & Co-Authors
von Ameln, Simon
Germany, Ulm
Universität Ulm
Germany, Koln
Universität zu Köln
Wang, Geng
United States, Los Angeles
University of California, Los Angeles
Boulouiz, Redouane
Morocco, Casablanca
Institut Pasteur du Maroc
Rutherford, Mark A.
Germany, Gottingen
Universitätsmedizin Göttingen
Smith, Geoffrey M.
United States, Los Angeles
David Geffen School of Medicine at Ucla
Li, Yun
Germany, Koln
Universität zu Köln
Pogoda, Hans Martin
Germany, Koln
Universität zu Köln
Nürnberg, Gudrun
Germany, Koln
Medizinische Fakultät
Stiller, Barbara
Germany, Ulm
Universität Ulm
Germany, Koln
Universität zu Köln
Volk, Alexander E.
Germany, Ulm
Universität Ulm
Germany, Koln
Universität zu Köln
Borck, Guntram
Germany, Ulm
Universität Ulm
Germany, Koln
Universität zu Köln
Hong, Jason S.
United States, Los Angeles
David Geffen School of Medicine at Ucla
Goodyear, Richard
United Kingdom, Brighton
University of Sussex
Abidi, Omar
Morocco, Casablanca
Institut Pasteur du Maroc
Nürnberg, Peter
Germany, Koln
Universität zu Köln
Germany, Koln
Medizinische Fakultät
Hofmann, Kay
Germany, Koln
Universität zu Köln
Richardson, Guy
United Kingdom, Brighton
University of Sussex
Hammerschmidt, Matthias
Germany, Koln
Universität zu Köln
Moser, Tobias
Germany, Gottingen
Universitätsmedizin Göttingen
Germany, Gottingen
Georg-august-universität Göttingen
Wollnik, Bernd
Germany, Koln
Universität zu Köln
Koehler, Carla M.
United States, Los Angeles
University of California, Los Angeles
Teitell, Michael A.
United States, Los Angeles
David Geffen School of Medicine at Ucla
United States, Los Angeles
University of California, Los Angeles
Barakat, Abdelhamid
Morocco, Casablanca
Institut Pasteur du Maroc
Kubisch, Christian
Germany, Ulm
Universität Ulm
Germany, Koln
Universität zu Köln
Statistics
Citations: 83
Authors: 24
Affiliations: 9
Identifiers
Doi:
10.1016/j.ajhg.2012.09.002
ISSN:
00029297
e-ISSN:
15376605
Research Areas
Cancer
Disability
Genetics And Genomics