Doublet decoding of tRNASer3 demonstrates plasticity of ribosomal decoding center
(2025) In Nature Communications 16(1).- 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... (More)
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.
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- author
- Krishnaswamy, Shruthi ; Akbar, Shirin ; Larsson, Daniel S.D. ; Chen, Yang LU and Selmer, Maria
- organization
- publishing date
- 2025-12
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Communications
- volume
- 16
- issue
- 1
- article number
- 5402
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:40571681
- scopus:105009248886
- ISSN
- 2041-1723
- DOI
- 10.1038/s41467-025-61016-5
- language
- English
- LU publication?
- yes
- id
- 83ffa650-882f-47c5-9f3d-ffbe1ec295cf
- date added to LUP
- 2025-10-27 10:12:59
- date last changed
- 2025-11-10 11:41:17
@article{83ffa650-882f-47c5-9f3d-ffbe1ec295cf,
abstract = {{<p>Frameshifts can be caused by specific combinations of tRNA and mRNA. The wildtype AGC-decoding E. coli tRNA<sup>Ser3</sup><sub>GCU</sub> 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 tRNA<sup>Ser3</sup> 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.</p>}},
author = {{Krishnaswamy, Shruthi and Akbar, Shirin and Larsson, Daniel S.D. and Chen, Yang and Selmer, Maria}},
issn = {{2041-1723}},
language = {{eng}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Nature Communications}},
title = {{Doublet decoding of tRNA<sup>Ser3</sup> demonstrates plasticity of ribosomal decoding center}},
url = {{http://dx.doi.org/10.1038/s41467-025-61016-5}},
doi = {{10.1038/s41467-025-61016-5}},
volume = {{16}},
year = {{2025}},
}