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

Document Type

Article

Publication Date

7-25-2014

JAX Source

Science 2014 Jul 25; 345(6195):455-9.

Volume

345

Issue

6195

First Page

455

Last Page

459

ISSN

1095-9203

PMID

25061210

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. Science 2014 Jul 25; 345(6195):455-9.

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