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Doublet decoding of tRNASer3 demonstrates plasticity of ribosomal decoding center

Author

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  • Shruthi Krishnaswamy

    (P.O. Box 596
    Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC))

  • Shirin Akbar

    (P.O. Box 596)

  • Daniel S. D. Larsson

    (P.O. Box 596)

  • Yang Chen

    (P.O. Box 596
    P.O. Box 118)

  • Maria Selmer

    (P.O. Box 596)

Abstract

Frameshifts can be caused by specific combinations of tRNA and mRNA. The wildtype AGC-decoding E. coli tRNASer3GCU has been shown to induce −1 ribosomal frameshifting on GCA alanine codons, and proposed to read a two-base codon instead of a canonical triplet. However, it has remained unclear whether this type of non-cognate decoding can be accommodated by the ribosome. Here, we perform single-particle cryo-EM reconstructions on E. coli 70S ribosomes with the frameshift-inducing tRNASer3 bound to the non-cognate GCA codon or the cognate AGC codon in the ribosomal A site. The structures demonstrate that doublet decoding is made possible when A1493, the conserved monitoring base in 16S rRNA, mimics a first codon base, forming a Hoogsteen base pair with U36 from the anticodon and stacking with the mRNA. This interaction pushes the first two bases of the A-site codon in position for base pairing with C35 and G34 of the anticodon.

Suggested Citation

  • Shruthi Krishnaswamy & Shirin Akbar & Daniel S. D. Larsson & Yang Chen & Maria Selmer, 2025. "Doublet decoding of tRNASer3 demonstrates plasticity of ribosomal decoding center," Nature Communications, Nature, vol. 16(1), pages 1-6, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61016-5
    DOI: 10.1038/s41467-025-61016-5
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