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The effect of tRNA structure and codon context on translation efficiency and fidelity

13.06.2024 12:30 pm 2:00 pm Joint Microbiological Colloquium Kelly T. Hughes

Speaker: Kelly T. Hughes (University of Utah)

Host: Samuel Wagner

Date & Time: 13.06.2024 | 12:30 – 2 p.m.

Venue:  Lecture hall 3M07, GUZ

Public event. No registration needed.


We have developed an in vivo mRNA translation speedometer assay in Salmonella that allows one to determine relative speeds that the ribosome translates codons and codon combinations. This assay allowed us to demonstrate that synonymous codons are often translated with a wide range of efficiencies. We also show that the efficiency of translating individual codons at the A-site of the ribosome can be significantly influenced by codons in the P- and E-codon sites. We call this the triplet-of-triplets genetic code for mRNA translation efficiency. We also devised a genetic selection for increased translation speeds through slow-translated codons and codon combinations. This resulted in the isolation of a single base substitution in the D-stem of LeuZ tRNA that allows LeuZ to translate the UCA (serine) codon. We propose that the slow GTP hydrolysis step catalyzed by translation elongation factor EF-Tu coupled to a transient conformational change in the tRNA structure provides a final fidelity check for cognate codon recognition to ensure correct codon recognition by tRNA.

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