Visualizing the Role of 2'-OH rRNA Methylations in the Human Ribosome Structure.
Fiche publication
Date publication
octobre 2018
Journal
Biomolecules
Auteurs
Membres identifiés du Cancéropôle Est :
Dr KLAHOLZ Bruno
Tous les auteurs :
Natchiar SK, Myasnikov AG, Hazemann I, Klaholz BP
Lien Pubmed
Résumé
Chemical modifications of RNA have recently gained new attention in biological sciences. They occur notably on messenger RNA (mRNA) and ribosomal RNA (rRNA) and are important for various cellular functions, but their molecular mechanism of action is yet to be understood in detail. Ribosomes are large ribonucleoprotein assemblies, which synthesize proteins in all organisms. Human ribosomes, for example, carry more than 200 modified nucleotides, which are introduced during biogenesis. Chemically modified nucleotides may appear to be only scarcely different from canonical nucleotides, but modifications such as methylations can in fact modulate their chemical and topological properties in the RNA and alter or modulate the overall translation efficiency of the ribosomes resulting in dysfunction of the translation machinery. Recent functional analysis and high-resolution ribosome structures have revealed a large repertoire of modification sites comprising different modification types. In this review, we focus on 2'--methylations (2'--Me) and discuss the structural insights gained through our recent cryo electron microscopy (cryo-EM) high-resolution structural analysis of the human ribosome, such as their locations and their influence on the secondary and tertiary structures of human rRNAs. The detailed analysis presented here reveals that ribose conformations of the rRNA backbone differ when the 2'-OH hydroxyl position is methylated, with 3'- conformations being the default and the 2'- conformations being characteristic in that the associated base is flipped-out. We compare currently known 2'--Me sites in human rRNAs evaluated using RiboMethSeq and cryo-EM structural analysis and discuss their involvement in several human diseases.
Mots clés
2′-O methylation, RNA, chemical modifications, human ribosome, ribosomal RNA, structural biology
Référence
Biomolecules. 2018 10 25;8(4):