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Title: Organisms with alternative genetic codes resolve unassigned codons via mistranslation and ribosomal rescue

Journal Article · · eLife
ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [3];  [3]; ORCiD logo [1]
  1. Yale Univ., New Haven, CT (United States). Dept. of Molecular, Cellular & Developmental Biology; Yale Univ., New Haven, CT (United States). Systems Biology Inst.
  2. Yale Univ., New Haven, CT (United States). Systems Biology Inst.; Yale Univ., New Haven, CT (United States). Dept. of Biomedical Engineering
  3. Yale Univ., New Haven, CT (United States). Systems Biology Inst.; Yale Univ., New Haven, CT (United States). School of Medicine. Dept. of Cellular & Molecular Physiology

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.

Research Organization:
Yale Univ., New Haven, CT (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
SC0010687; 152339.5055249.100
OSTI ID:
1479816
Alternate ID(s):
OSTI ID: 1479817; OSTI ID: 1628882
Journal Information:
eLife, Vol. 7; ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.Copyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 16 works
Citation information provided by
Web of Science

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Cited By (1)