Functional analysis of the AUG initiator codon context reveals novel conserved sequences that disfavor mRNA translation in eukaryotes

Abstract mRNA translation is a fundamental process for life. Selection of the translation initiation site (TIS) is crucial, as it establishes the correct open reading frame for mRNA decoding. Studies in vertebrate mRNAs discovered that a purine at −3 and a G at +4 (where A of the AUG initiator codon...

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Veröffentlicht in:Nucleic acids research 2024-02, Vol.52 (3), p.1064-1079
Hauptverfasser: Hernández, Greco, García, Alejandra, Weingarten-Gabbay, Shira, Mishra, Rishi Kumar, Hussain, Tanweer, Amiri, Mehdi, Moreno-Hagelsieb, Gabriel, Montiel-Dávalos, Angélica, Lasko, Paul, Sonenberg, Nahum
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Sprache:eng
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Zusammenfassung:Abstract mRNA translation is a fundamental process for life. Selection of the translation initiation site (TIS) is crucial, as it establishes the correct open reading frame for mRNA decoding. Studies in vertebrate mRNAs discovered that a purine at −3 and a G at +4 (where A of the AUG initiator codon is numbered + 1), promote TIS recognition. However, the TIS context in other eukaryotes has been poorly experimentally analyzed. We analyzed in vitro the influence of the −3, −2, −1 and + 4 positions of the TIS context in rabbit, Drosophila, wheat, and yeast. We observed that −3A conferred the best translational efficiency across these species. However, we found variability at the + 4 position for optimal translation. In addition, the Kozak motif that was defined from mammalian cells was only weakly predictive for wheat and essentially non-predictive for yeast. We discovered eight conserved sequences that significantly disfavored translation. Due to the big differences in translational efficiency observed among weak TIS context sequences, we define a novel category that we termed ‘barren AUG context sequences (BACS)’, which represent sequences disfavoring translation. Analysis of mRNA-ribosomal complexes structures provided insights into the function of BACS. The gene ontology of the BACS-containing mRNAs is presented. Graphical Abstract Graphical Abstract
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkad1152