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• W2147401901 abstract "Eukaryotic initiator tRNA (tRNA i ) contains several highly conserved unique sequence features, but their importance in accurate start codon selection was unknown. Here we show that conserved bases throughout tRNA i , from the anticodon stem to acceptor stem, play key roles in ensuring the fidelity of start codon recognition in yeast cells. Substituting the conserved G31:C39 base pair in the anticodon stem with different pairs reduces accuracy (the Sui − [suppressor of initiation codon] phenotype), whereas eliminating base pairing increases accuracy (the Ssu − [suppressor of Sui − ] phenotype). The latter defect is fully suppressed by a Sui − substitution of T-loop residue A54. These genetic data are paralleled by opposing effects of Sui − and Ssu − substitutions on the stability of methionylated tRNA i (Met-tRNA i ) binding (in the ternary complex [TC] with eIF2-GTP) to reconstituted preinitiation complexes (PICs). Disrupting the C3:G70 base pair in the acceptor stem produces a Sui − phenotype and also reduces the rate of TC binding to 40S subunits in vitro and in vivo. Both defects are suppressed by an Ssu − substitution in eIF1A that stabilizes the open/P OUT conformation of the PIC that exists prior to start codon recognition. Our data indicate that these signature sequences of tRNA i regulate accuracy by distinct mechanisms, promoting the open/P OUT conformation of the PIC (for C3:G70) or destabilizing the closed/P IN state (for G31:C39 and A54) that is critical for start codon recognition." @default.
• W2147401901 created "2016-06-24" @default.
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• W2147401901 date "2014-03-01" @default.
• W2147401901 modified "2023-10-13" @default.
• W2147401901 title "Conserved residues in yeast initiator tRNA calibrate initiation accuracy by regulating preinitiation complex stability at the start codon" @default.
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• W2147401901 doi "https://doi.org/10.1101/gad.236547.113" @default.
• W2147401901 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3950347" @default.
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• W2147401901 hasPublicationYear "2014" @default.
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