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Science. 2014 Jul 25;345(6195):455-9. doi: 10.1126/science.1249749.

RNA function. Ribosome stalling induced by mutation of a CNS-specific tRNA causes neurodegeneration.

Author information

1
Howard Hughes Medical Institute and The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
2
The Jackson Laboratory for Genomic Medicine, 263 Farmington Avenue, Farmington, CT 06030, USA.
3
The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
4
Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
5
Howard Hughes Medical Institute and The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA. susan.ackerman@jax.org.

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.

PMID:
25061210
PMCID:
PMC4281038
DOI:
10.1126/science.1249749
[Indexed for MEDLINE]
Free PMC Article

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