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Proc Natl Acad Sci U S A. 2017 Dec 5;114(49):12934-12939. doi: 10.1073/pnas.1707674114. Epub 2017 Nov 20.

Evidence for rRNA 2'-O-methylation plasticity: Control of intrinsic translational capabilities of human ribosomes.

Author information

1
Centre de Recherche en Cancérologie de Lyon, UMR, INSERM 1052, CNRS 5286, Centre Léon Bérard, F-69373 Lyon, France.
2
Institut des Sciences Pharmaceutiques et Biologiques, Université de Lyon, F-69003 Lyon, France.
3
Next-Generation Sequencing Core Facility, FR3209 Bioingénierie Moléculaire Cellulaire et Thérapeutique, CNRS, Lorraine University, F-54505 Vandoeuvre-les-Nancy, France.
4
Centre International de Recherche en Infectiologie, Université de Lyon, 69364 Lyon, France.
5
Ecole Normale Supérieure de Lyon, 69342 Lyon, France.
6
Institute for Integrative Biology of the Cell, Commissariat à l'Energie Atomique, CNRS, Université Paris-Sud, Université Paris-Saclay, 91190 Gif-sur-Yvette, France.
7
Laboratoire Biologie à Grande Échelle, Institut de Biosciences et Biotechnologies de Grenoble, Université Grenoble Alpes, Commissariat à l'énergie Atomique et aux Énergies Alternatives, INSERM, 38000 Grenoble, France.
8
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104 INSERM U 964, F-67404 Illkirch, France.
9
Ingénierie Moléculaire et Physiopathologie Articulaire, UMR7365, CNRS, Université de Lorraine, F-54505 Vandoeuvre-les-Nancy, France.
10
Centre de Recherche en Cancérologie de Lyon, UMR, INSERM 1052, CNRS 5286, Centre Léon Bérard, F-69373 Lyon, France; frederic.catez@lyon.unicancer.fr jean-jacques.diaz@lyon.unicancer.fr.

Abstract

Ribosomal RNAs (rRNAs) are main effectors of messenger RNA (mRNA) decoding, peptide-bond formation, and ribosome dynamics during translation. Ribose 2'-O-methylation (2'-O-Me) is the most abundant rRNA chemical modification, and displays a complex pattern in rRNA. 2'-O-Me was shown to be essential for accurate and efficient protein synthesis in eukaryotic cells. However, whether rRNA 2'-O-Me is an adjustable feature of the human ribosome and a means of regulating ribosome function remains to be determined. Here we challenged rRNA 2'-O-Me globally by inhibiting the rRNA methyl-transferase fibrillarin in human cells. Using RiboMethSeq, a nonbiased quantitative mapping of 2'-O-Me, we identified a repertoire of 2'-O-Me sites subjected to variation and demonstrate that functional domains of ribosomes are targets of 2'-O-Me plasticity. Using the cricket paralysis virus internal ribosome entry site element, coupled to in vitro translation, we show that the intrinsic capability of ribosomes to translate mRNAs is modulated through a 2'-O-Me pattern and not by nonribosomal actors of the translational machinery. Our data establish rRNA 2'-O-Me plasticity as a mechanism providing functional specificity to human ribosomes.

KEYWORDS:

2′-O-methylation; RNA epigenetics; fibrillarin; ribosomal RNA; translational control

PMID:
29158377
PMCID:
PMC5724255
DOI:
10.1073/pnas.1707674114
[Indexed for MEDLINE]
Free PMC Article

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