Hernández, G and GarcÃa, A and Weingarten-Gabbay, S and Mishra, RK and Hussain, T and Amiri, M and Moreno-Hagelsieb, G and Montiel-Dávalos, A and Lasko, P and Sonenberg, N (2024) Functional analysis of the AUG initiator codon context reveals novel conserved sequences that disfavor mRNA translation in eukaryotes. In: Nucleic Acids Research, 52 (3). pp. 1064-1079.
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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. © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.
| Item Type: | Journal Article |
|---|---|
| Publication: | Nucleic Acids Research |
| Publisher: | Oxford University Press |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Keywords: | creatine kinase; initiation factor 1A; messenger RNA, amino acid sequence; Article; codon; conserved sequence; Drosophila; Drosophila melanogaster; eukaryote; gene expression; gene silencing; in vitro study; Leporidae; molecular docking; nonhuman; RNA translation; single nucleotide polymorphism; start codon; translation initiation; Triticum aestivum; yeast |
| Department/Centre: | Division of Biological Sciences > Molecular Reproduction, Development & Genetics |
| Date Deposited: | 09 Apr 2024 10:44 |
| Last Modified: | 09 Apr 2024 10:44 |
| URI: | https://eprints.iisc.ac.in/id/eprint/84690 |
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