Abstract
In higher eukaryotes, transfer RNAs (tRNAs) with the same anticodon are encoded by multiple nuclear genes, and little is known about how mutations in these genes affect translation and cellular homeostasis. Similarly, the surveillance systems that respond to such defects in higher eukaryotes are not clear. Here, we discover that loss of GTPBP2, a novel binding partner of the ribosome recycling protein Pelota, in mice with a mutation in a tRNA gene that is specifically expressed in the central nervous system causes ribosome stalling and widespread neurodegeneration. Our results not only define GTPBP2 as a ribosome rescue factor but also unmask the disease potential of mutations in nuclear-encoded tRNA genes.
Copyright © 2014, American Association for the Advancement of Science.
Publication types
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Research Support, American Recovery and Reinvestment Act
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cell Nucleus / genetics
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Cerebellum / metabolism*
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Cerebellum / pathology
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Endonucleases
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GTP-Binding Proteins / genetics
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GTP-Binding Proteins / metabolism*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Microfilament Proteins / genetics
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Microfilament Proteins / metabolism*
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Neurodegenerative Diseases / genetics*
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Point Mutation
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Protein Biosynthesis / genetics*
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RNA Splice Sites / genetics
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RNA, Transfer, Arg / genetics*
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Ribosomes / metabolism*
Substances
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Cell Cycle Proteins
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Microfilament Proteins
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RNA Splice Sites
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RNA, Transfer, Arg
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Endonucleases
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Pelo protein, mouse
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GTP-Binding Proteins
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GTPBP2 protein, mouse