Blasticidin S inhibits mammalian translation and enhances production of protein encoded by nonsense mRNA

Kyle T Powers, Flint R Stevenson-Jones, Sathish Yadav Kadapalakere, Josh C Bufton, Ufuk Borucu, Dakang Shen, Christiane H Berger-Schaffitzel*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Deciphering translation is of paramount importance for the understanding of many diseases, and antibiotics played a pivotal role in this endeavour. Blasticidin S (BlaS) targets translation by binding to the peptidyl transferase center of the large ribosomal subunit. Using biochemical, structural, and cellular approaches, we show here that BlaS inhibits both translation elongation and termination in Mammalia. Bound to mammalian terminating ribosomes, BlaS distorts the 3’CCA tail of the P-site tRNA to a larger extent than previously reported for bacterial ribosomes, thus delaying both, peptide bond formation and peptidyl-tRNA hydrolysis. While BlaS does not inhibit stop codon recognition by the eukaryotic release factor1 (eRF1), it interferes with eRF1’s accommodation into the peptidyl transferase center and subsequent peptide release. In human cells, BlaS inhibits nonsense-mediated mRNA decay and, at subinhibitory concentrations, modulates translation dynamics at premature termination codons leading to enhanced protein production.
Original languageEnglish
Pages (from-to)7665-7679
Number of pages15
JournalNucleic Acids Research
Issue number13
Early online date22 Jun 2021
Publication statusPublished - 21 Jul 2021

Bibliographical note

Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.

Structured keywords

  • Bristol BioDesign Institute


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