Doublet decoding of tRNASer3 demonstrates plasticity of ribosomal decoding center
Abstract Frameshifts can be caused by specific combinations of tRNA and mRNA. The wildtype AGC-decoding E. coli tRNASer3 GCU 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 uncle...
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| Language: | English |
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Nature Portfolio
2025-06-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61016-5 |
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| author | Shruthi Krishnaswamy Shirin Akbar Daniel S. D. Larsson Yang Chen Maria Selmer |
| author_facet | Shruthi Krishnaswamy Shirin Akbar Daniel S. D. Larsson Yang Chen Maria Selmer |
| author_sort | Shruthi Krishnaswamy |
| collection | DOAJ |
| description | Abstract Frameshifts can be caused by specific combinations of tRNA and mRNA. The wildtype AGC-decoding E. coli tRNASer3 GCU 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. |
| format | Article |
| id | doaj-art-02e3fd0e99644ac8bdaffd296cfae7b0 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-02e3fd0e99644ac8bdaffd296cfae7b02025-08-20T03:27:10ZengNature PortfolioNature Communications2041-17232025-06-011611610.1038/s41467-025-61016-5Doublet decoding of tRNASer3 demonstrates plasticity of ribosomal decoding centerShruthi Krishnaswamy0Shirin Akbar1Daniel S. D. Larsson2Yang Chen3Maria Selmer4Department of Cell and Molecular Biology, Uppsala University, BMC, P.O. Box 596Department of Cell and Molecular Biology, Uppsala University, BMC, P.O. Box 596Department of Cell and Molecular Biology, Uppsala University, BMC, P.O. Box 596Department of Cell and Molecular Biology, Uppsala University, BMC, P.O. Box 596Department of Cell and Molecular Biology, Uppsala University, BMC, P.O. Box 596Abstract Frameshifts can be caused by specific combinations of tRNA and mRNA. The wildtype AGC-decoding E. coli tRNASer3 GCU 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.https://doi.org/10.1038/s41467-025-61016-5 |
| spellingShingle | Shruthi Krishnaswamy Shirin Akbar Daniel S. D. Larsson Yang Chen Maria Selmer Doublet decoding of tRNASer3 demonstrates plasticity of ribosomal decoding center Nature Communications |
| title | Doublet decoding of tRNASer3 demonstrates plasticity of ribosomal decoding center |
| title_full | Doublet decoding of tRNASer3 demonstrates plasticity of ribosomal decoding center |
| title_fullStr | Doublet decoding of tRNASer3 demonstrates plasticity of ribosomal decoding center |
| title_full_unstemmed | Doublet decoding of tRNASer3 demonstrates plasticity of ribosomal decoding center |
| title_short | Doublet decoding of tRNASer3 demonstrates plasticity of ribosomal decoding center |
| title_sort | doublet decoding of trnaser3 demonstrates plasticity of ribosomal decoding center |
| url | https://doi.org/10.1038/s41467-025-61016-5 |
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