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Title2'-O-Methylation maintains ribosome structural and translation integrity.
Journal, issue, pagesMol Cell, Vol. 86, Issue 8, Page 1495-11510.e7, Year 2026
Publish dateApr 16, 2026
AuthorsYu Zhao / Jay Rai / Lauren N Cohen / Yuerong Shu / Chong Xu / Hemant Goswami / Xin Chen / Hong Jin / Virginie Marchand / Yuri Motorin / Homa Ghalei / Hong Li /
PubMed AbstractIn eukaryotic ribosomes, ∼2% of RNA nucleotides undergo 2'-O-methylation, a conserved cellular mechanism thought to be critical for maintaining and regulating translation. Here, we use ribosome ...In eukaryotic ribosomes, ∼2% of RNA nucleotides undergo 2'-O-methylation, a conserved cellular mechanism thought to be critical for maintaining and regulating translation. Here, we use ribosome profiling, translation assays, proteomics, and high-resolution structural analyses to show that loss of native 2'-O-methylation in yeast ribosomes disproportionally affects the translation of ribosomal protein transcripts, driven by changes in codon usage and recognition of structured RNA. Translation reprogramming by the hypomethylated ribosomes is supported by reduced thermostability and high-resolution evidence of altered ribosomal structures and conformations. Consistent with the roles of the affected proteins in sustaining cellular fitness, hypomethylated ribosomes under stress exhibit a selective loss of downregulated proteins and misassembly associated with methylation loss. Our data provide structural and mechanistic insights into how 2'-O-methylation supports ribosome integrity and mediates cellular stress responses.
External linksMol Cell / PubMed:41928510 / PubMed Central
MethodsEM (single particle)
Resolution1.75 Å
Structure data

71745

9pn5

EMDB-71745, PDB-9pn5:
Composite map of hypomethylated 80S ribosome treated with hygromycin B
Method: EM (single particle) / Resolution: 1.75 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-K:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-HOH:
WATER

Source
  • saccharomyces cerevisiae by4741 (yeast)
KeywordsRIBOSOME / 2'-O-methylation / rRNA modification

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