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Functional analysis of the AUG initiator codon context reveals novel conserved sequences that disfavor mRNA translation in eukaryotes.
Hernández, Greco; García, Alejandra; Weingarten-Gabbay, Shira; Mishra, Rishi Kumar; Hussain, Tanweer; Amiri, Mehdi; Moreno-Hagelsieb, Gabriel; Montiel-Dávalos, Angélica; Lasko, Paul; Sonenberg, Nahum.
Afiliação
  • Hernández G; mRNA and Cancer Laboratory, Unit of Biomedical Research on Cancer, National Institute of Cancer (INCan), Mexico City 14080, Mexico.
  • García A; mRNA and Cancer Laboratory, Unit of Biomedical Research on Cancer, National Institute of Cancer (INCan), Mexico City 14080, Mexico.
  • Weingarten-Gabbay S; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Mishra RK; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA.
  • Hussain T; Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA.
  • Amiri M; Department of Developmental Biology and Genetics, Indian Institute of Science, Bengaluru-560012, India.
  • Moreno-Hagelsieb G; Department of Developmental Biology and Genetics, Indian Institute of Science, Bengaluru-560012, India.
  • Montiel-Dávalos A; Department of Biochemistry and Goodman Cancer Institute. McGill University., Montreal, QC H3A 1A3, Canada.
  • Lasko P; Department of Biology, Wilfrid Laurier University. 75 University Ave. W, Waterloo, ON N2L 3C5, Canada.
  • Sonenberg N; mRNA and Cancer Laboratory, Unit of Biomedical Research on Cancer, National Institute of Cancer (INCan), Mexico City 14080, Mexico.
Nucleic Acids Res ; 52(3): 1064-1079, 2024 Feb 09.
Article em En | MEDLINE | ID: mdl-38038264
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Biossíntese de Proteínas / Sequência Conservada / Códon de Iniciação Limite: Animals Idioma: En Revista: Nucleic Acids Res Ano de publicação: 2024 Tipo de documento: Article País de afiliação: México País de publicação: Reino Unido
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Biossíntese de Proteínas / Sequência Conservada / Códon de Iniciação Limite: Animals Idioma: En Revista: Nucleic Acids Res Ano de publicação: 2024 Tipo de documento: Article País de afiliação: México País de publicação: Reino Unido