Organisms with alternative genetic codes resolve unassigned codons via mistranslation and ribosomal rescue
Abstract
Organisms possessing genetic codes with unassigned codons raise the question of how cellular machinery resolves such codons and how this could impact horizontal gene transfer. Here, we use a genomically recoded Escherichia coli to examine how organisms address translation at unassigned UAG codons, which obstruct propagation of UAG-containing viruses and plasmids. Using mass spectrometry, we show that recoded organisms resolve translation at unassigned UAG codons via near-cognate suppression, dramatic frameshifting from at least −3 to +19 nucleotides, and rescue by ssrA-encoded tmRNA, ArfA, and ArfB. We then demonstrate that deleting tmRNA restores expression of UAG-ending proteins and propagation of UAG-containing viruses and plasmids in the recoded strain, indicating that tmRNA rescue and nascent peptide degradation is the cause of impaired virus and plasmid propagation. The ubiquity of tmRNA homologs suggests that genomic recoding is a promising path for impairing horizontal gene transfer and conferring genetic isolation in diverse organisms.
- Authors:
-
[1];
[2];
[3];
[1]
- Department of Molecular, Cellular & Developmental Biology, Yale University, New Haven, United States, Systems Biology Institute, Yale University, West Haven, United States
- Systems Biology Institute, Yale University, West Haven, United States, Department of Biomedical Engineering, Yale University, New Haven, United States
- Systems Biology Institute, Yale University, West Haven, United States, Department of Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, United States
- Publication Date:
- Research Org.:
- Yale Univ., New Haven, CT (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1479816
- Alternate Identifier(s):
- OSTI ID: 1479817; OSTI ID: 1628882
- Grant/Contract Number:
- 152339.5055249.100; SC0010687
- Resource Type:
- Published Article
- Journal Name:
- eLife
- Additional Journal Information:
- Journal Name: eLife Journal Volume: 7; Journal ID: ISSN 2050-084X
- Publisher:
- eLife Sciences Publications, Ltd.
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Life Sciences & Biomedicine - Other Topics
Citation Formats
Ma, Natalie Jing, Hemez, Colin F., Barber, Karl W., Rinehart, Jesse, and Isaacs, Farren J. Organisms with alternative genetic codes resolve unassigned codons via mistranslation and ribosomal rescue. United States: N. p., 2018.
Web. doi:10.7554/eLife.34878.
Ma, Natalie Jing, Hemez, Colin F., Barber, Karl W., Rinehart, Jesse, & Isaacs, Farren J. Organisms with alternative genetic codes resolve unassigned codons via mistranslation and ribosomal rescue. United States. https://doi.org/10.7554/eLife.34878
Ma, Natalie Jing, Hemez, Colin F., Barber, Karl W., Rinehart, Jesse, and Isaacs, Farren J. Tue .
"Organisms with alternative genetic codes resolve unassigned codons via mistranslation and ribosomal rescue". United States. https://doi.org/10.7554/eLife.34878.
@article{osti_1479816,
title = {Organisms with alternative genetic codes resolve unassigned codons via mistranslation and ribosomal rescue},
author = {Ma, Natalie Jing and Hemez, Colin F. and Barber, Karl W. and Rinehart, Jesse and Isaacs, Farren J.},
abstractNote = {Organisms possessing genetic codes with unassigned codons raise the question of how cellular machinery resolves such codons and how this could impact horizontal gene transfer. Here, we use a genomically recoded Escherichia coli to examine how organisms address translation at unassigned UAG codons, which obstruct propagation of UAG-containing viruses and plasmids. Using mass spectrometry, we show that recoded organisms resolve translation at unassigned UAG codons via near-cognate suppression, dramatic frameshifting from at least −3 to +19 nucleotides, and rescue by ssrA-encoded tmRNA, ArfA, and ArfB. We then demonstrate that deleting tmRNA restores expression of UAG-ending proteins and propagation of UAG-containing viruses and plasmids in the recoded strain, indicating that tmRNA rescue and nascent peptide degradation is the cause of impaired virus and plasmid propagation. The ubiquity of tmRNA homologs suggests that genomic recoding is a promising path for impairing horizontal gene transfer and conferring genetic isolation in diverse organisms.},
doi = {10.7554/eLife.34878},
journal = {eLife},
number = ,
volume = 7,
place = {United States},
year = {2018},
month = {10}
}
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