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TitleImpacts of ribosomal RNA sequence variation on gene expression and phenotype.
Journal, issue, pagesPhilos Trans R Soc Lond B Biol Sci, Vol. 380, Issue 1921, Page 20230379, Year 2025
Publish dateMar 6, 2025
AuthorsGriffin A Welfer / Ryan A Brady / S Kundhavai Natchiar / Zoe L Watson / Emily J Rundlet / Jose L Alejo / Anand P Singh / Nitish K Mishra / Roger B Altman / Scott C Blanchard /
PubMed AbstractSince the framing of the Central Dogma, it has been speculated that physically distinct ribosomes within cells may influence gene expression and cellular physiology. While heterogeneity in ribosome ...Since the framing of the Central Dogma, it has been speculated that physically distinct ribosomes within cells may influence gene expression and cellular physiology. While heterogeneity in ribosome composition has been reported in bacteria, protozoans, fungi, zebrafish, mice and humans, its functional implications remain actively debated. Here, we review recent evidence demonstrating that expression of conserved variant ribosomal DNA (rDNA) alleles in bacteria, mice and humans renders their actively translating ribosome pool intrinsically heterogeneous at the level of ribosomal RNA (rRNA). In this context, we discuss reports that nutrient limitation-induced stress in leads to changes in variant rRNA allele expression, programmatically altering transcription and cellular phenotype. We highlight that cells expressing ribosomes from distinct operons exhibit distinct drug sensitivities, which can be recapitulated and potentially rationalized by subtle perturbations in ribosome structure or in their dynamic properties. Finally, we discuss evidence that differential expression of variant rDNA alleles results in different populations of ribosome subtypes within mammalian tissues. These findings motivate further research into the impacts of rRNA heterogeneities on ribosomal function and predict that strategies targeting distinct ribosome subtypes may hold therapeutic potential.This article is part of the discussion meeting issue 'Ribosome diversity and its impact on protein synthesis, development and disease'.
External linksPhilos Trans R Soc Lond B Biol Sci / PubMed:40045785 / PubMed Central
MethodsEM (single particle)
Resolution2.2 - 2.4 Å
Structure data

48830

9n2b

EMDB-48830, PDB-9n2b:
Impacts of ribosomal RNA sequence variation on gene expression and phenotype: Cryo-EM structure of the rrsB ribosome (BBB-70S)
Method: EM (single particle) / Resolution: 2.2 Å

48831

9n2c

EMDB-48831, PDB-9n2c:
Impacts of ribosomal RNA sequence variation on gene expression and phenotype: Cryo-EM structure of the rrsH ribosome (HBB-70S)
Method: EM (single particle) / Resolution: 2.4 Å

Chemicals

ChemComp-PUT:
1,4-DIAMINOBUTANE

ChemComp-SPD:
SPERMIDINE

ChemComp-MG:
Unknown entry

ChemComp-K:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-FME:
N-FORMYLMETHIONINE

Source
  • escherichia coli k-12 (bacteria)
  • escherichia coli bl21 (bacteria)
KeywordsRIBOSOME / Translation / Transcription / rDNA / rRNA / Cryo-EM

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