Ribosomal 18S rRNA base pairs with mRNA during eukaryotic translation initiation

Franck Martin, Jean-François Ménétret, Angelita Simonetti, Alexander G. Myasnikov, Quentin Vicens, Lydia Prongidi-Fix, S. Kundhavai Natchiar, Bruno P. Klaholz () and Gilbert Eriani ()
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Franck Martin: Architecture et Réactivité de l’ARN, Centre National de la Recherche Scientifique (CNRS) UPR9002, Institute of Molecular and Cellular Biology (IBMC), Université de Strasbourg
Jean-François Ménétret: Centre for Integrative Biology (CBI), IGBMC (Institute of Genetics and of Molecular and Cellular Biology)
Angelita Simonetti: Architecture et Réactivité de l’ARN, Centre National de la Recherche Scientifique (CNRS) UPR9002, Institute of Molecular and Cellular Biology (IBMC), Université de Strasbourg
Alexander G. Myasnikov: Centre for Integrative Biology (CBI), IGBMC (Institute of Genetics and of Molecular and Cellular Biology)
Quentin Vicens: Architecture et Réactivité de l’ARN, Centre National de la Recherche Scientifique (CNRS) UPR9002, Institute of Molecular and Cellular Biology (IBMC), Université de Strasbourg
Lydia Prongidi-Fix: Architecture et Réactivité de l’ARN, Centre National de la Recherche Scientifique (CNRS) UPR9002, Institute of Molecular and Cellular Biology (IBMC), Université de Strasbourg
S. Kundhavai Natchiar: Centre for Integrative Biology (CBI), IGBMC (Institute of Genetics and of Molecular and Cellular Biology)
Bruno P. Klaholz: Centre for Integrative Biology (CBI), IGBMC (Institute of Genetics and of Molecular and Cellular Biology)
Gilbert Eriani: Architecture et Réactivité de l’ARN, Centre National de la Recherche Scientifique (CNRS) UPR9002, Institute of Molecular and Cellular Biology (IBMC), Université de Strasbourg

Nature Communications, 2016, vol. 7, issue 1, 1-7

Abstract: Abstract Eukaryotic mRNAs often contain a Kozak sequence that helps tether the ribosome to the AUG start codon. The mRNA of histone H4 (h4) does not undergo classical ribosome scanning but has evolved a specific tethering mechanism. The cryo-EM structure of the rabbit ribosome complex with mouse h4 shows that the mRNA forms a folded, repressive structure at the mRNA entry site on the 40S subunit next to the tip of helix 16 of 18S ribosomal RNA (rRNA). Toe-printing and mutational assays reveal that an interaction exists between a purine-rich sequence in h4 mRNA and a complementary UUUC sequence of helix h16. Together the present data establish that the h4 mRNA harbours a sequence complementary to an 18S rRNA sequence which tethers the mRNA to the ribosome to promote proper start codon positioning, complementing the interactions of the 40S subunit with the Kozak sequence that flanks the AUG start codon.

Date: 2016
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DOI: 10.1038/ncomms12622

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