Talk abstracts
Talk on Saturday 09:45-10:00am submitted by Katharine Maschhoff
GCN2 monitors mRNA translation termination
Katharine R. Maschhoff (Department of Biochemistry and Molecular Biology, Mayo Clinic), Kailey Worner (Department of Biochemistry and Molecular Biology, Mayo Clinic), Gabrielle M. Schuh (Department of Biochemistry and Molecular Biology, Mayo Clinic), Wenqian Hu (Department of Biochemistry and Molecular Biology, Mayo Clinic)
Abstract:
Controlling mRNA translation is critical for proper protein production. Although translation initiation and elongation regulations are becoming increasingly clear, whether and how translation termination is monitored remains poorly understood. Using an acute protein degradation system coupled with phenotypic rescue via ectopic expression, here we show that the impaired translation termination reaction leads to rapid activation of GCN2, resulting in eIF2a phosphorylation and inhibition of translation initiation, which occurs prior to ribosome collisions. Ribosome profiling analyses reveal that GCN2 monitors terminating ribosomes and prevents ribosome collisions and mitigates translation readthrough when translation termination is compromised. This rapid activation of GCN2 by compromised translation termination occurs in both stem and somatic cells, and in mouse and human cells. These results reveal a conserved surveillance mechanism of translation termination.
Keywords: GCN2, Translation Termination, Ribosome Collision