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      2′-O-Methylation of Ribosomal RNA: Towards an Epitranscriptomic Control of Translation?

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          Abstract

          Ribosomal RNA (rRNA) undergoes post-transcriptional modification of over 200 nucleotides, predominantly 2′-O-methylation (2′-O-Me). 2′-O-Methylation protects RNA from hydrolysis and modifies RNA strand flexibility but does not contribute to Watson-Crick base pairing. The contribution of 2′-O-Me to the translational capacity of ribosomes has been established. Yet, how 2′-O-Me participates in ribosome biogenesis and ribosome functioning remains unclear. The development of 2′-O-Me quantitative mapping methods has contributed to the demonstration that these modifications are not constitutive but rather provide heterogeneity to the ribosomal population. Moreover, recent advances in ribosome structure analysis and in vitro translation assays have proven, for the first time, that 2′-O-Me contributes to regulating protein synthesis. This review highlights the recent data exploring the impact of 2′-O-Me on ribosome structure and function, and the emerging idea that the rRNA epitranscriptome is involved in translational control.

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          Most cited references71

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          Heterogeneous Ribosomes Preferentially Translate Distinct Subpools of mRNAs Genome-wide.

          Emerging studies have linked the ribosome to more selective control of gene regulation. However, an outstanding question is whether ribosome heterogeneity at the level of core ribosomal proteins (RPs) exists and enables ribosomes to preferentially translate specific mRNAs genome-wide. Here, we measured the absolute abundance of RPs in translating ribosomes and profiled transcripts that are enriched or depleted from select subsets of ribosomes within embryonic stem cells. We find that heterogeneity in RP composition endows ribosomes with differential selectivity for translating subpools of transcripts, including those controlling metabolism, cell cycle, and development. As an example, mRNAs enriched in binding to RPL10A/uL1-containing ribosomes are shown to require RPL10A/uL1 for their efficient translation. Within several of these transcripts, this level of regulation is mediated, at least in part, by internal ribosome entry sites. Together, these results reveal a critical functional link between ribosome heterogeneity and the post-transcriptional circuitry of gene expression.
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            Site-specific ribose methylation of preribosomal RNA: a novel function for small nucleolar RNAs.

            Eukaryotic cells contain many fibrillarin-associated small nucleolar RNAs (snoRNAs) that possess long complementarities to mature rRNAs. Characterization of 21 novel antisense snoRNAs from human cells followed by genetic depletion and reconstitution studies on yeast U24 snoRNA provides evidence that this class of snoRNAs is required for site-specific 2'-O-methylation of preribosomal RNA (pre-rRNA). Antisense sno-RNAs function through direct base-pairing interactions with pre-rRNA. The antisense element, together with the D or D' box of the snoRNA, provide the information necessary to select the target nucleotide for the methyltransfer reaction. The conclusion that sno-RNAs function in covalent modification of the sugar moieties of ribonucleotides demonstrates that eukaryotic small nuclear RNAs have a more versatile cellular function than earlier anticipated.
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              rRNA modifications and ribosome function.

              The development of three-dimensional maps of the modified nucleotides in the ribosomes of Escherichia coli and yeast has revealed that most (approximately 95% in E. coli and 60% in yeast) occur in functionally important regions. These include the peptidyl transferase centre, the A, P and E sites of tRNA- and mRNA binding, the polypeptide exit tunnel, and sites of subunit-subunit interaction. The correlations suggest that many ribosome functions benefit from nucleotide modification.
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                Author and article information

                Journal
                Biomolecules
                Biomolecules
                biomolecules
                Biomolecules
                MDPI
                2218-273X
                03 October 2018
                December 2018
                : 8
                : 4
                : 106
                Affiliations
                Univ Lyon, Université Claude Bernard Lyon 1, INSERM U1052, CNRS UMR5286, Cancer Research Center of Lyon, 69008 Lyon, France; piero.lomonaco@ 123456lyon.unicancer.fr (P.L.M.); virginie.marcel@ 123456lyon.unicancer.fr (V.M.)
                Author notes
                Author information
                https://orcid.org/0000-0002-9557-8221
                https://orcid.org/0000-0002-7914-4319
                https://orcid.org/0000-0001-8255-9091
                Article
                biomolecules-08-00106
                10.3390/biom8040106
                6316387
                30282949
                4bba6e6b-7424-47f8-8373-213e43b13166
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 17 August 2018
                : 27 September 2018
                Categories
                Review

                2′-o-methylation,ribosomal rna,fibrillarin,snornp,ribosome heterogeneity,mrna translation

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