GTPBP1 resolves paused ribosomes to maintain neuronal homeostasis.

ABSTRACT: Ribosome-associated quality control pathways respond to defects in translational elongation to recycle arrested ribosomes and degrade aberrant polypeptides and mRNAs. Loss of a tRNA gene leads to ribosomal pausing that is resolved by the translational GTPase GTPBP2, and in its absence causes neuron death. Here, we show that loss of the homologous protein GTPBP1 during tRNA deficiency in the mouse brain also leads to codon-specific ribosome pausing and neurodegeneration, suggesting that these non-redundant GTPases function in the same pathway to mitigate ribosome pausing. As observed in Gtpbp2^-/- mice (Ishimura et al., 2016), GCN2-mediated activation of the integrated stress response (ISR) was apparent in the Gtpbp1^-/- brain. We observed decreased mTORC1

SUBMITTER: Terrey M 

PROVIDER: S-EPMC7665888 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature