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TitleAn RNA modification prevents extended codon-anticodon interactions from facilitating +1 frameshifting.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 7392, Year 2025
Publish dateAug 11, 2025
AuthorsEvelyn M Kimbrough / Ha An Nguyen / Haixing Li / Jacob M Mattingly / Nevette A Bailey / Wei Ning / Howard Gamper / Ya-Ming Hou / Ruben L Gonzalez / Christine M Dunham /
PubMed AbstractRNA post-transcriptional modifications act by stabilizing the functional conformations of RNA. While their role in messenger RNA (mRNA) decoding is well established, it is less clear how transfer RNA ...RNA post-transcriptional modifications act by stabilizing the functional conformations of RNA. While their role in messenger RNA (mRNA) decoding is well established, it is less clear how transfer RNA (tRNA) modifications outside the anticodon contribute to tRNA stability and accurate protein synthesis. Absence of such modifications causes translation errors, including mRNA frameshifting. By integrating single-molecule fluorescence resonance energy transfer and cryogenic electron microscopy, we demonstrate that the N-methylguanosine (mG) modification at position 37 of Escherichia coli tRNA is necessary and sufficient for modulating the conformational energy of this tRNA on the ribosome so as to suppress +1 frameshifting otherwise induced by this tRNA. Six structures of E. coli ribosomal complexes carrying tRNA lacking mG37 show this tRNA forms four and even five codon-anticodon base pairs as it moves into the +1 frame, allowing direct visualization of the long-standing hypothesis that a four base pair codon-anticodon can form during +1 frameshifting.
External linksNat Commun / PubMed:40789848 / PubMed Central
MethodsEM (single particle)
Resolution2.9 - 4.0 Å
Structure data

42495

8urm

EMDB-42495, PDB-8urm:
E. coli 70S ribosome with unmodified tRNAPro(GGG) bound to slippery P-site CCC-C codon and tRNAVal(UAC) in the A site
Method: EM (single particle) / Resolution: 3.0 Å

42541

8utj

EMDB-42541, PDB-8utj:
E. coli 70S ribosome with unmodified lys-tRNAPro(GGG) bound to slippery P-site CCC-C codon in the 0 frame
Method: EM (single particle) / Resolution: 3.5 Å

42714

8ux8

EMDB-42714, PDB-8ux8:
E. coli 70S ribosome with unmodified Lys-tRNAPro(GGG) bound to slippery P-site CCC-C codon in the +1 mRNA reading frame
Method: EM (single particle) / Resolution: 3.6 Å

42721

8uxb

EMDB-42721, PDB-8uxb:
E. coli 70S ribosome with unmodified P/E-tRNAPro(GGG) bound to slippery P-site CCC-C codon
Method: EM (single particle) / Resolution: 2.9 Å

42840

8uzg

EMDB-42840, PDB-8uzg:
E. coli 70S ribosome with unmodified e*/E-tRNAPro(GGG) bound to slippery P-site CCC-C codon
Method: EM (single particle) / Resolution: 3.7 Å

42852

8v03

EMDB-42852, PDB-8v03:
E. coli 70S ribosome with unmodified P/E-tRNAPro(GGG) bound to slippery P-site CCC-C codon
Method: EM (single particle) / Resolution: 4.0 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-HOH:
WATER

ChemComp-LYS:
LYSINE

Source
  • escherichia coli (E. coli)
KeywordsRIBOSOME / 70S ribosome / tRNA / mRNA / frameshift

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