Mutations in the mouse gene n-Tr20, which encodes a tRNA specifically expressed in the central nervous system, can slow translation at AGA codons by increasing ribosome pausing, thereby promoting neuronal death, a new study in Science shows. However, analyses of multiple strains of mice revealed that the neurodegeneration only manifests when the n-Tr20 mutation co-occurs with a loss-of-function mutation in GTP-binding protein 2 (Gtpbp2). Co-immunoprecipitation and affinity capture experiments showed that GTPBP2 directly interacts with the ribosome recycling protein Pelota.
References
Ishimura, R. et al. Ribosome stalling induced by mutation of a CNS-specific tRNA causes neurodegeneration. Science 345, 455–459 (2014)
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Koch, L. Loss of rescue factor unmasks epistatic mutation. Nat Rev Genet 15, 572 (2014). https://doi.org/10.1038/nrg3807
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DOI: https://doi.org/10.1038/nrg3807