9RUC

WT-HEK 80S ribosome bound to H2B mRNA (WT-H2B)

This is a non-PDB format compatible entry.

Summary for 9RUC

• Entry DOI: 10.2210/pdb9ruc/pdb
• EMDB information: 54269
• Descriptor: 5S rRNA, Large ribosomal subunit protein uL6, Large ribosomal subunit protein uL16, ... (87 entities in total)
• Functional Keywords: 80s ribosome, h2b mrna, human, es26, wt-hek, ribosome
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 80
• Total formula weight: 3815597.14

Authors

Hiregange, D.G.,Fraticelli, D.,Bashan, A.,Yonath, A.,Dikstein, R. (deposition date: 2025-07-03, release date: 2026-05-13)

Primary citation

Fraticelli, D.,Hiregange, D.G.,Weiss, B.,Ogran, A.,Havkin-Solomon, T.,Roman, I.M.,Bashan, A.,Yonath, A.,Dikstein, R.
Structural and molecular basis of specialized translation mediated by the ribosome mRNA-binding channel.
Nat Commun, 2026

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) 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.

PubMed: 42056121
DOI: 10.1038/s41467-026-72263-5

Experimental method

ELECTRON MICROSCOPY (2.5 Å)