RNA Therapeutics Institute
Biochemistry | Structural Biology
Accurate translation termination by release factors (RFs) is critical for the integrity of cellular proteomes. Premature termination on sense codons, for example, results in truncated proteins, whose accumulation could be detrimental to the cell. Nevertheless, some sense codons are prone to triggering premature termination, but the structural basis for this is unclear. To investigate premature termination, we determined a cryo-EM structure of the Escherichia coli 70S ribosome bound with RF1 in response to a UAU (Tyr) sense codon. The structure reveals that RF1 recognizes a UAU codon similarly to a UAG stop codon, suggesting that sense codons induce premature termination because they structurally mimic a stop codon. Hydrophobic interaction between the nucleobase of U3 (the third position of the UAU codon) and conserved Ile 196 in RF1 is important for misreading the UAU codon. Analyses of RNA binding in ribonucleoprotein complexes or by amino acids reveal that Ile-U packing is a frequent protein-RNA binding motif with key functional implications. We discuss parallels with eukaryotic translation termination by the release factor eRF1.
translation release factor, translation regulation, ribosome structure, ribosome function, RNA–protein interaction, 70S ribosome, hot-spot sense codon, hydrophobic interactions, near-stop codon
Rights and Permissions
© 2018 Svidritskiy et al. Publisher PDF posted after 12 months as allowed by the publisher's author rights policy at http://www.jbc.org/site/misc/edpolicy.xhtml#copyright.
DOI of Published Version
J Biol Chem. 2018 Jun 25. pii: AW118.003232. doi: 10.1074/jbc.AW118.003232. Link to article on publisher's site
The Journal of biological chemistry
Svidritskiy, Egor; Demo, Garbriel; and Korostelev, Andrei A., "Mechanism of premature translation termination on a sense codon" (2018). RNA Therapeutics Institute Publications. 34.