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-Structure paper
| タイトル | Structural and molecular basis of specialized translation mediated by the ribosome mRNA-binding channel. |
|---|---|
| ジャーナル・号・ページ | Nat Commun, Year 2026 |
| 掲載日 | 2026年4月29日 |
著者 | Davide Fraticelli / Disha Gajanan Hiregange / Benjamin Weiss / Ariel Ogran / Tal Havkin-Solomon / Irene Martinez Roman / Anat Bashan / Ada Yonath / Rivka Dikstein / ![]() |
| PubMed 要旨 | The ribosome mRNA channel is central to translation, yet its role in regulatory mechanisms remains unclear. Using cryo-EM of human ribosomal complexes bound to Kozak and TISU mRNAs from wild-type (WT) ...The ribosome mRNA channel is central to translation, yet its role in regulatory mechanisms remains unclear. Using cryo-EM of human ribosomal complexes bound to Kozak and TISU mRNAs from wild-type (WT) and RPS26/eS26 mutant (RPS26dC) cells, we demonstrate that both RPS26/eS26 and mRNA adopt distinct conformations, explaining the opposing effects of RPS26dC on their activity. Translatome studies of WT and RPS26dC reveal AUG-context-dependent changes in 48S and 80S initiation complexes and slower scanning. Downregulated mRNAs are enriched for specific AUG-upstream nucleotides and a -1-cytosine contacting 18S rRNA G1207, an interaction lost in RPS26dC. Strongly affected transcripts include replication-dependent histones, which, despite short 5'UTRs and suboptimal Kozak, exhibit robust translation activity that is RPS26/eS26-dependent. We identify a translational enhancer in the H2B 5'UTR (-16 to -9) overlapping predicted RPS26/eS26-binding sites, with a distinct ribosome-bound conformation. Exploiting these features, we engineered a high-efficiency translational cassette with minimal leaky scanning. These findings underscore the role of the ribosome's mRNA channel in selective translation and its therapeutic potential. |
リンク | Nat Commun / PubMed:42056121 |
| 手法 | EM (単粒子) |
| 解像度 | 2.5 - 3.0 Å |
| 構造データ | EMDB-54265, PDB-9ru7: EMDB-54266, PDB-9ru8: EMDB-54267, PDB-9ru9: EMDB-54268, PDB-9rua: EMDB-54269, PDB-9ruc: |
| 化合物 | ![]() ChemComp-K: ![]() ChemComp-MG: ![]() ChemComp-C: ![]() ChemComp-NA: ![]() ChemComp-ZN: ![]() ChemComp-HYG: ![]() ChemComp-HOH: ![]() ChemComp-SPD: ![]() ChemComp-SAC: ![]() ChemComp-AME: ![]() ChemComp-MET: ![]() ChemComp-ANM: |
| 由来 |
|
キーワード | RIBOSOME / 80S Ribosome / Kozak mRNA / Human / eS26 / WT-HEK / TISU mRNA / RPS26dC / H2B mRNA |
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