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Blasticidin S inhibits mammalian translation and enhances production of protein encoded by nonsense mRNA
- Source :
- Nucleic Acids Research, Powers, K T, Stevenson-Jones, F R, Yadav Kadapalakere, S, Bufton, J C, Borucu, U, Shen, D & Berger-Schaffitzel, C H 2021, ' Blasticidin S inhibits mammalian translation and enhances production of protein encoded by nonsense mRNA ', Nucleic Acids Research, vol. 49, no. 13, pp. 7665-7679 . https://doi.org/10.1093/nar/gkab532
- Publication Year :
- 2021
- Publisher :
- Oxford University Press (OUP), 2021.
-
Abstract
- 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 factor 1 (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.
- Subjects :
- Peptidyl transferase
AcademicSubjects/SCI00010
Peptide Chain Elongation, Translational
Ribosome
chemistry.chemical_compound
RNA, Transfer
Large ribosomal subunit
RNA and RNA-protein complexes
Genetics
Humans
RNA, Messenger
Protein Synthesis Inhibitors
biology
Bristol BioDesign Institute
Cryoelectron Microscopy
Nucleosides
Translation (biology)
Peptide Chain Termination, Translational
Ribosome Subunits, Large, Eukaryotic
Stop codon
Nonsense Mediated mRNA Decay
Blasticidin S
Cell biology
chemistry
Transfer RNA
biology.protein
Peptides
Release factor
Ribosomes
HeLa Cells
Peptide Termination Factors
Subjects
Details
- ISSN :
- 13624962 and 03051048
- Volume :
- 49
- Database :
- OpenAIRE
- Journal :
- Nucleic Acids Research
- Accession number :
- edsair.doi.dedup.....9fa3653edf7d8f052a97802afee7f568