The structure of the human 80S ribosome at 1.9 Å resolution reveals the molecular role of chemical modifications and ions in RNA by Samuel Holvec & Charles Barchet & Antony Lechner & Léo Fréchin & S. Nimali T. Silva & Isabelle Hazemann & Philippe Wolff & Ottilie Loeffelholz & Bruno P. Klaholz instant download

The structure of the human 80S ribosome at 1.9 Å resolution reveals the molecular role of chemical modifications and ions in RNA by Samuel Holvec & Charles Barchet & Antony Lechner & Léo Fréchin & S. Nimali T. Silva & Isabelle Hazemann & Philippe Wolff & Ottilie Loeffelholz & Bruno P. Klaholz instant download

Nature Structural & Molecular Biology | Volume 31 | August 2024 | 1251–1264
The ribosomal RNA of the human protein synthesis machinery comprisesnumerous chemical modifications that are introduced during ribosome
biogenesis. Here we present the 1.9 Å resolution cryo electron microscopy
structure of the 80S human ribosome resolving numerous new ribosomal
RNA modifications and functionally important ions such as Zn2+, K+
and Mg2+, including their associated individual water molecules. The
2′-O-methylation, pseudo-uridine and base modifications were confirmed
by mass spectrometry, resulting in a complete investigation of the >230
sites, many of which could not be addressed previously. They choreograph
key interactions within the RNA and at the interface with proteins, including
at the ribosomal subunit interfaces of the fully assembled 80S ribosome.
Uridine isomerization turns out to be a key mechanism for U–A base pair
stabilization in RNA in general. The structural environment of chemical
modifications and ions is primordial for the RNA architecture of the mature
human ribosome, hence providing a structural framework to address their
role in healthy states and in human diseases.