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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • Methylation
  • Protein Biosynthesis*
  • RNA, Ribosomal / metabolism*


  • Chromosomal Proteins, Non-Histone
  • RNA, Ribosomal
  • fibrillarin