Blasticidin S inhibits mammalian translation and enhances production of protein encoded by nonsense mRNA
| العنوان: | Blasticidin S inhibits mammalian translation and enhances production of protein encoded by nonsense mRNA |
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| المؤلفون: | Matthias W. Hentze, K.N. Sathish Yadav, Gabriele Neu-Yilik, Beate Amthor, Joshua C. Bufton, Jonas Philipp Becker, Dakang Shen, Kyle T. Powers, Andreas E. Kulozik, Flint Stevenson-Jones, Ufuk Borucu, Christiane Schaffitzel, Daria Lavysh |
| المصدر: | 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/gkab532Test |
| بيانات النشر: | Oxford University Press (OUP), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| تدمد: | 1362-4962 0305-1048 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9fa3653edf7d8f052a97802afee7f568Test https://doi.org/10.1093/nar/gkab532Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9fa3653edf7d8f052a97802afee7f568 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13624962 03051048 |
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