@article{86a695a379f04217ad8e7daf6423f58a,
title = "Stop codon context influences genome-wide stimulation of termination codon readthrough by aminoglycosides",
abstract = "Stop codon readthrough (SCR) occurs when the ribosome miscodes at a stop codon. Such readthrough events can be therapeutically desirable when a premature termination codon (PTC) is found in a critical gene. To study SCR in vivo in a genome-wide manner, we treated mammalian cells with aminoglycosides and performed ribosome profiling. We find that in addition to stimulating readthrough of PTCs, aminoglycosides stimulate readthrough of normal termination codons (NTCs) genome-wide. Stop codon identity, the nucleotide following the stop codon, and the surrounding mRNA sequence context all influence the likelihood of SCR. In comparison to NTCs, downstream stop codons in 3{\textquoteleft}UTRs are recognized less efficiently by ribosomes, suggesting that targeting of critical stop codons for readthrough may be achievable without general disruption of translation termination. Finally, we find that G418-induced miscoding alters gene expression with substantial effects on translation of histone genes, selenoprotein genes, and S-adenosylmethionine decarboxylase (AMD1).",
author = "Wangen, {Jamie R.} and Rachel Green",
note = "Funding Information: We thank Phil Thomas and Michael Torres for help in working with Calu-6 cells, David Bedwell for providing a Nano Luciferase construct, Boris Zinshteyn for careful reading of the manuscript and help with statistics and data analysis, Colin Wu for extensive help with coding and data analysis, and all members of the Green lab for helpful discussion and guidance throughout the study. We thank David Mohr and the Johns Hopkins Genetic Resources Core Facility for sequencing assistance. This work was supported by the Cystic Fibrosis Foundation (GREEN16G0). J.R.W. was supported by an NIH training grant for a portion of this study (T32 GM007445). Funding Information: We thank Phil Thomas and Michael Torres for help in working with Calu-6 cells, David Bedwell for providing a Nano Luciferase construct, Boris Zinshteyn for careful reading of the manuscript and help with statistics and data analysis, Colin Wu for extensive help with coding and data analysis, and all members of the Green lab for helpful discussion and guidance throughout the study. We thank David Mohr and the Johns Hopkins Genetic Resources Core Facility for sequencing assistance. This work was supported by the Cystic Fibros is Foundation (GREEN16G0). J.R.W. was supported by an NIH training grant for a portion of this study (T32 GM007445). Publisher Copyright: {\textcopyright} 2020, eLife Sciences Publications Ltd. All rights reserved.",
year = "2020",
month = jan,
doi = "10.7554/eLife.52611",
language = "English (US)",
volume = "9",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications Ltd",
}