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Nat Commun. 2016 Aug 24;7:12622. doi: 10.1038/ncomms12622.

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

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Architecture et Réactivité de l'ARN, Centre National de la Recherche Scientifique (CNRS) UPR9002, Institute of Molecular and Cellular Biology (IBMC), Université de Strasbourg, 15 rue René Descartes, 67084 Strasbourg, France.
Department of Integrated Structural Biology, Centre for Integrative Biology (CBI), IGBMC (Institute of Genetics and of Molecular and Cellular Biology), 1 rue Laurent Fries, 67404 Illkirch, France.
CNRS UMR 7104, 67404 Illkirch, France.
Institut National de la Santé et de la Recherche Médicale (INSERM) U964, 67404 Illkirch, France.
Université de Strasbourg, 67081 Strasbourg, France.


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.

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