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| Title | Structural and molecular basis of specialized translation mediated by the ribosome mRNA-binding channel. |
|---|---|
| Journal, issue, pages | Nat Commun, Vol. 17, Issue 1, Year 2026 |
| Publish date | Apr 29, 2026 |
Authors | Davide Fraticelli / Disha Gajanan Hiregange / Benjamin Weiss / Ariel Ogran / Tal Havkin-Solomon / Irene Martinez Roman / Anat Bashan / Ada Yonath / Rivka Dikstein / ![]() |
| PubMed Abstract | 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. |
External links | Nat Commun / PubMed:42056121 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.4 - 3.3 Å |
| Structure data | EMDB-54265, PDB-9ru7: EMDB-54266, PDB-9ru8: EMDB-54267, PDB-9ru9: EMDB-54268, PDB-9rua: EMDB-54269, PDB-9ruc: ![]() EMDB-55120: Focus refined 60S map of WT-HEK 80S ribosome bound to Kozak mRNA (WT-Kozak) ![]() EMDB-55121: Focus refined 40S map of WT-HEK 80S ribosome bound to Kozak mRNA (WT-Kozak) ![]() EMDB-55126: WT-HEK 80S ribosome bound to Kozak mRNA (WT-Kozak) consensus map ![]() EMDB-55215: WT-HEK 80S ribosome bound to TISU mRNA (WT-TISU) consensus map ![]() EMDB-55216: Focus refined 60S map of WT-HEK 80S ribosome bound to TISU mRNA (WT-TISU) ![]() EMDB-55217: Focus refined 40S map of WT-HEK 80S ribosome bound to TISU mRNA (WT-TISU) ![]() EMDB-55218: Focus refined 40S map of RPS26dC HEK mutant 80S ribosome bound to Kozak mRNA (RPS26dC-Kozak) ![]() EMDB-55219: RPS26dC HEK mutant 80S ribosome bound to Kozak mRNA (RPS26dC-Kozak) consensus map ![]() EMDB-55220: Focus refined 60S map of RPS26dC HEK mutant 80S ribosome bound to Kozak mRNA (RPS26dC-Kozak) ![]() EMDB-55226: Focus refined 40S map of RPS26dC HEK mutant 80S ribosome bound to TISU mRNA (RPS26dC-TISU) ![]() EMDB-55227: Focus refined 60S map of RPS26dC HEK mutant 80S ribosome bound to TISU mRNA (RPS26dC-TISU) ![]() EMDB-55228: RPS26dC HEK mutant 80S ribosome bound to TISU mRNA (RPS26dC-TISU) consensus map ![]() EMDB-55300: WT-HEK 80S ribosome bound to H2B mRNA (WT-H2B) consensus map ![]() EMDB-55301: Focus refined 60S map of WT-HEK 80S ribosome bound to H2B mRNA (WT-H2B) ![]() EMDB-55302: Focus refined 40S map of WT-HEK 80S ribosome bound to H2B mRNA (WT-H2B) |
| Chemicals | ![]() ChemComp-K: ![]() ChemComp-MG: ![]() ChemComp-C: ![]() ChemComp-NA: ![]() ChemComp-ZN: ![]() ChemComp-HYG: ![]() ChemComp-HOH: ![]() ChemComp-SPD: ![]() ChemComp-SAC: ![]() ChemComp-AME: ![]() ChemComp-MET: ![]() ChemComp-ANM: |
| Source |
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Keywords | RIBOSOME / 80S Ribosome / Kozak mRNA / Human / eS26 / WT-HEK / TISU mRNA / RPS26dC / H2B mRNA |
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homo sapiens (human)
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