Visualizing the Role of 2’-OH rRNA Methylations in the Human Ribosome Structure
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 larg...
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| Format: | Article |
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MDPI AG
2018-10-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/8/4/125 |
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| author | S. Kundhavai Natchiar Alexander G. Myasnikov Isabelle Hazemann Bruno P. Klaholz |
| author_facet | S. Kundhavai Natchiar Alexander G. Myasnikov Isabelle Hazemann Bruno P. Klaholz |
| author_sort | S. Kundhavai Natchiar |
| collection | DOAJ |
| description | 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′-<i>O</i>-methylations (2′-<i>O</i>-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′-<i>endo</i> conformations being the default and the 2′-<i>endo</i> conformations being characteristic in that the associated base is flipped-out. We compare currently known 2′-<i>O</i>-Me sites in human rRNAs evaluated using RiboMethSeq and cryo-EM structural analysis and discuss their involvement in several human diseases. |
| first_indexed | 2024-12-19T23:34:03Z |
| format | Article |
| id | doaj.art-24e8706a4f684455bf1ea7b76cc377e1 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-12-19T23:34:03Z |
| publishDate | 2018-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-24e8706a4f684455bf1ea7b76cc377e12022-12-21T20:01:39ZengMDPI AGBiomolecules2218-273X2018-10-018412510.3390/biom8040125biom8040125Visualizing the Role of 2’-OH rRNA Methylations in the Human Ribosome StructureS. Kundhavai Natchiar0Alexander G. Myasnikov1Isabelle Hazemann2Bruno P. Klaholz3Centre for Integrative Biology (CBI), Department of Integrated Structural Biology, IGBMC, CNRS, Inserm, Université de Strasbourg, 1 rue Laurent Fries, 67404 Illkirch, FranceCentre for Integrative Biology (CBI), Department of Integrated Structural Biology, IGBMC, CNRS, Inserm, Université de Strasbourg, 1 rue Laurent Fries, 67404 Illkirch, FranceCentre for Integrative Biology (CBI), Department of Integrated Structural Biology, IGBMC, CNRS, Inserm, Université de Strasbourg, 1 rue Laurent Fries, 67404 Illkirch, FranceCentre for Integrative Biology (CBI), Department of Integrated Structural Biology, IGBMC, CNRS, Inserm, Université de Strasbourg, 1 rue Laurent Fries, 67404 Illkirch, FranceChemical 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′-<i>O</i>-methylations (2′-<i>O</i>-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′-<i>endo</i> conformations being the default and the 2′-<i>endo</i> conformations being characteristic in that the associated base is flipped-out. We compare currently known 2′-<i>O</i>-Me sites in human rRNAs evaluated using RiboMethSeq and cryo-EM structural analysis and discuss their involvement in several human diseases.https://www.mdpi.com/2218-273X/8/4/125RNAchemical modificationsribosomal RNA2′-<i>O</i> methylationhuman ribosomestructural biology |
| spellingShingle | S. Kundhavai Natchiar Alexander G. Myasnikov Isabelle Hazemann Bruno P. Klaholz Visualizing the Role of 2’-OH rRNA Methylations in the Human Ribosome Structure Biomolecules RNA chemical modifications ribosomal RNA 2′-<i>O</i> methylation human ribosome structural biology |
| title | Visualizing the Role of 2’-OH rRNA Methylations in the Human Ribosome Structure |
| title_full | Visualizing the Role of 2’-OH rRNA Methylations in the Human Ribosome Structure |
| title_fullStr | Visualizing the Role of 2’-OH rRNA Methylations in the Human Ribosome Structure |
| title_full_unstemmed | Visualizing the Role of 2’-OH rRNA Methylations in the Human Ribosome Structure |
| title_short | Visualizing the Role of 2’-OH rRNA Methylations in the Human Ribosome Structure |
| title_sort | visualizing the role of 2 oh rrna methylations in the human ribosome structure |
| topic | RNA chemical modifications ribosomal RNA 2′-<i>O</i> methylation human ribosome structural biology |
| url | https://www.mdpi.com/2218-273X/8/4/125 |
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