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

• Published in: Nature communications Vol. 7; no. 1; p. 12622
• Main Authors: Martin, Franck, Ménétret, Jean-François, Simonetti, Angelita, Myasnikov, Alexander G., Vicens, Quentin, Prongidi-Fix, Lydia, Natchiar, S. Kundhavai, Klaholz, Bruno P., Eriani, Gilbert
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.08.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 101/28; 38/70; 38/77; 631/337/574/1789; 631/535/1258/1259; 82; 82/1; Animals; Base Pairing; Base Sequence; Biochemistry, Molecular Biology; Cell cycle; Cellular biology; Codon, Initiator; Histones - biosynthesis; Histones - genetics; Humanities and Social Sciences; Life Sciences; Mice; Models, Molecular; Molecular biology; multidisciplinary; Mutation; Nucleic Acid Conformation; Peptide Chain Initiation, Translational - genetics; Proteins; Rabbits; Ribonucleic acid; Ribosomes - chemistry; Ribosomes - genetics; Ribosomes - metabolism; RNA; RNA, Messenger - chemistry; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Ribosomal, 18S - chemistry; RNA, Ribosomal, 18S - genetics; RNA, Ribosomal, 18S - metabolism; Science; Science (multidisciplinary); Transfer RNA; France
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms12622

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. Prokaryotic translation initiation involves mRNA-ribosomal RNA base pairing interactions. Here, the authors provide evidence for a similar base pairing interactions occurring between the human h4 mRNA and helix 16 of the small subunit rRNA to position the correct AUG codon in the decoding site.