Open AccessThe context of the ribosome binding site in mRNAs defines specificity of action of kasugamycin, an inhibitor of translation initiation
Author(s) -
Yan Zhang,
Nikolay A. Aleksashin,
Dorota Klepacki,
Caleb M. Anderson,
Nora VázquezLaslop,
Carol A. Gross,
Alexander S. Mankin
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2118553119
Subject(s) - ribosome , biology , transfer rna , eukaryotic translation , messenger rna , protein biosynthesis , translational frameshift , ribosomal rna , translation (biology) , microbiology and biotechnology , genetics , rna , gene
Significance Several antibiotics targeting the large ribosomal subunit interfere with translation in a context-specific manner, preventing ribosomes from polymerizing specific amino acid sequences. Here, we reveal kasugamycin as a small ribosomal subunit-targeting antibiotic whose action depends on the sequence context of the untranslated messenger RNA (mRNA) segments. We show that kasugamycin-induced ribosomal arrest at the start codons of the genes and the resulting inhibition of gene expression depend on the nature of the mRNA nucleotide immediately preceding the start codon and on the proximity of the stop codon of the upstream cistron. Our findings underlie the importance of mRNA context for the action of protein synthesis inhibitors and might help to guide the development of better antibiotics.