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9H74

Late-stage 48S Initiation Complex with eIF3 (LS48S-eIF3 IC) guided by the trans-RNA

This is a non-PDB format compatible entry.
Summary for 9H74
Entry DOI10.2210/pdb9h74/pdb
EMDB information51911
DescriptorInitiator methionylated tRNA, 40S ribosomal protein S4, Ribosomal protein S5, ... (52 entities in total)
Functional Keywords48s late-stage initiation complex, programmable mrna translation initiation, trans-rna, activation of mrna translation, translation
Biological sourceOryctolagus cuniculus
More
Total number of polymer chains51
Total formula weight2140721.30
Authors
Nguyen, T.T.,Hashem, Y.,Rocha, R.E.O.,Boissier, F.,Qian, S.B.,Jia, L.,Uematsu, S.,Gu, Y.,Shi, S. (deposition date: 2024-10-25, release date: 2025-12-10)
Primary citationJia, L.,Nguyen, T.T.,Uematsu, S.,Gu, Y.,Shi, S.,Hashem, Y.,Qian, S.B.
Programmable initiation of mRNA translation by trans-RNA.
Nat.Biotechnol., 2025
Cited by
PubMed Abstract: Several approaches exist to silence genes, but few tools are available to activate individual mRNAs for translation inside cells. Guiding ribosomes to specific start codons without altering the original sequence remains a formidable task. Here we design capped trans-RNAs capable of directing ribosomes to specific initiation sites on individual mRNAs when the trans-cap is positioned near the target start codon. Structural and biochemical data suggest that the capped trans-RNA facilitates ribosome loading and scanning on the target mRNA through a synergistic mechanism involving alternative cap recognition. The trans-RNA also acts independently of the cap on the target mRNA, enabling translation of circular RNAs lacking internal ribosome entry sites. We apply trans-RNAs in vivo to achieve programmable alternative translation of endogenous genes in mouse liver. Finally, we provide the evidence for the existence of natural transcripts that, similarly to exogenous trans-RNAs, activate translation of endogenous mRNAs.
PubMed: 41272315
DOI: 10.1038/s41587-025-02897-1
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (2.9 Å)
Structure validation

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