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.
Nat Commun. 2016 Aug 24;7:12622. 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.
真核生物的 mRNA 通常含有一个 Kozak 序列,有助于将核糖体与 AUG 起始密码子结合。组蛋白 H4 (h4) 的 mRNA 不经历经典的核糖体扫描,但已经进化出一种特定的连接机制。兔核糖体与小鼠 h4 的冷冻电镜结构表明,mRNA 在 40S 亚基的 mRNA 入口处形成一个折叠的、抑制性结构,位于 18S rRNA(rRNA)螺旋 16 尖端的旁边。足迹印迹和突变分析表明,h4 mRNA 中的一个嘌呤丰富序列与 h16 螺旋的互补 UUUC 序列之间存在相互作用。综上所述,这些数据表明 h4 mRNA 具有与 18S rRNA 序列互补的序列,该序列将 mRNA 连接到核糖体上,以促进正确的起始密码子定位,补充了 40S 亚基与侧翼 AUG 起始密码子的 Kozak 序列的相互作用。