title: RNA function. Ribosome stalling induced by mutation of a CNS-specific tRNA causes neurodegeneration.
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.
authors: Howard Hughes Medical Institute and The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
authors: Ryuta
authors: R
authors: Ishimura
authors: Howard Hughes Medical Institute and The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
authors: Gabor
authors: G
authors: Nagy
authors: The Jackson Laboratory for Genomic Medicine, 263 Farmington Avenue, Farmington, CT 06030, USA.
authors: Ivan
authors: I
authors: Dotu
authors: The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Huihao
authors: H
authors: Zhou
authors: The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Xiang-Lei
authors: XL
authors: Yang
authors: The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Paul
authors: P
authors: Schimmel
authors: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
authors: Satoru
authors: S
authors: Senju
authors: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
authors: Yasuharu
authors: Y
authors: Nishimura
authors: The Jackson Laboratory for Genomic Medicine, 263 Farmington Avenue, Farmington, CT 06030, USA.
authors: Jeffrey H
authors: JH
authors: Chuang
authors: Howard Hughes Medical Institute and The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA. susan.ackerman@jax.org.
authors: Susan L
authors: SL
authors: Ackerman
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000235:genetics; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology; D004720:Endonucleases; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000235:genetics*; D017354:Point Mutation; D014176:Protein Biosynthesis / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics; D012347:RNA, Transfer, Arg / Q000235:genetics*; D012270:Ribosomes / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D008840:Microfilament Proteins; D022821:RNA Splice Sites; D012347:RNA, Transfer, Arg; D004720:Endonucleases; C000590334:Pelo protein, mouse; D019204:GTP-Binding Proteins; C000590335:GTPBP2 protein, mouse