Abstract The recognition mechanism of Kozak mRNA, typically comprising purines in the - 3 and +4 positions flanking the AUG start codon, has remained enigmatic for decades. To address this fundamental function in eukaryotes during translation initiation, we analysed the cryo-EM structures of human 48S preinitiation complexes with mRNA point mutations. They reveal a fan-like intercalation of the pre-codon triplet into the 18S ribosomal RNA (rRNA), while the -3 purine as opposed to the pyrimidine in the non-Kozak co…

Summary The ribosomal RNA of the human protein synthesis machinery comprises numerous chemical modifications that are introduced during ribosome biogenesis. We present the 1.9 Å resolution cryo-EM structure of the 80S human ribosome resolving numerous new rRNA modifications and functionally important ions such as Zn 2+ , K + and Mg 2+ including their associated individual water molecules. 2’-O-methylation, pseudo-uridine and base modifications were confirmed by mass spectrometry resulting in a complete investigati…

The human 80S ribosome is the cellular nucleoprotein nanomachine in charge of protein synthesis that is profoundly affected during cancer transformation by oncogenic proteins and provides cancerous proliferating cells with proteins and therefore biomass. Indeed, cancer is associated with an increase in ribosome biogenesis and mutations in several ribosomal proteins genes are found in ribosomopathies, which are congenital diseases that display an elevated risk of cancer. Ribosomes and their biogenesis therefore rep…