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Biomolecules 2018, 8(4), 125;

Visualizing the Role of 2’-OH rRNA Methylations in the Human Ribosome Structure

Centre for Integrative Biology (CBI), Department of Integrated Structural Biology, IGBMC, CNRS, Inserm, Université de Strasbourg, 1 rue Laurent Fries, 67404 Illkirch, France
Institute of Genetics and of Molecular and Cellular Biology (IGBMC), 1 rue Laurent Fries, 67404 Illkirch, France
Centre National de la Recherche Scientifique (CNRS), UMR 7104, 67404 Illkirch, France
Institut National de la Santé et de la Recherche Médicale (Inserm), U964, 67404 Illkirch, France
Faculté des Sciences de la Vie, Université de Strasbourg, 67404 Illkirch, France
Author to whom correspondence should be addressed.
Received: 20 August 2018 / Revised: 10 October 2018 / Accepted: 18 October 2018 / Published: 25 October 2018
(This article belongs to the Special Issue rRNA Biology)
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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′-O-methylations (2′-O-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′-endo conformations being the default and the 2′-endo conformations being characteristic in that the associated base is flipped-out. We compare currently known 2′-O-Me sites in human rRNAs evaluated using RiboMethSeq and cryo-EM structural analysis and discuss their involvement in several human diseases. View Full-Text
Keywords: RNA; chemical modifications; ribosomal RNA; 2′-O methylation; human ribosome; structural biology RNA; chemical modifications; ribosomal RNA; 2′-O methylation; human ribosome; structural biology

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Natchiar, S.K.; Myasnikov, A.G.; Hazemann, I.; Klaholz, B.P. Visualizing the Role of 2’-OH rRNA Methylations in the Human Ribosome Structure. Biomolecules 2018, 8, 125.

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