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. Author manuscript; available in PMC: 2018 Nov 1.
Published in final edited form as: Neuron. 2017 Nov 1;96(3):616–637. doi: 10.1016/j.neuron.2017.09.057

Figure 4. Ribosome stalling-mediated neurodegeneration.

Figure 4

A processing mutation in n-Tr20, an arginine tRNA gene, in C57BL/6J mice significantly reduces the pool of tRNAArgUCU available for translation. This reduction leads to increased ribosome pausing on cognate AGA codons. GTPBP2 and Pelota play a role in the resolution of these paused ribosomes, and ribosome recycling may be accompanied by the degradation of the nascent protein and of the mRNA. In the absence of GTPBP2, ribosome pausing at the AGA codons is not resolved, leading to neurodegeneration. Ribosome stalling activates the integrated stress response (ISR) via the eIF2a kinase GCN2, and neurodegeneration is exacerbated in the absence of ISR activation.