Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes
Overview
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In eukaryotes, accurate protein synthesis relies on a family of translational GTPases that pair with specific decoding factors to decipher the mRNA code on ribosomes. We present structures of the mammalian ribosome engaged with decoding factor⋅GTPase complexes representing intermediates of translation elongation (aminoacyl-tRNA⋅eEF1A), termination (eRF1⋅eRF3), and ribosome rescue (Pelota⋅Hbs1l). Comparative analyses reveal that each decoding factor exploits the plasticity of the ribosomal decoding center to differentially remodel ribosomal proteins and rRNA. This leads to varying degrees of large-scale ribosome movements and implies distinct mechanisms for communicating information from the decoding center to each GTPase. Additional structural snapshots of the translation termination pathway reveal the conformational changes that choreograph the accommodation of decoding factors into the peptidyl transferase center. Our results provide a structural framework for how different states of the mammalian ribosome are selectively recognized by the appropriate decoding factor⋅GTPase complex to ensure translational fidelity.
Synthetic lethality of mRNA quality control complexes in cancer.
Prindle V, Richardson A, Sher K, Kongpachith S, Kentala K, Petiwala S Nature. 2025; 638(8052):1095-1103.
PMID: 39910291 PMC: 11864970. DOI: 10.1038/s41586-024-08398-6.
Ribosomal A-site interactions with near-cognate tRNAs drive stop codon readthrough.
capkova Pavlikova Z, Miletinova P, Roithova A, Pospisilova K, Zahonova K, Kachale A Nat Struct Mol Biol. 2025; .
PMID: 39806023 DOI: 10.1038/s41594-024-01450-z.
Capturing eukaryotic ribosome dynamics in situ at high resolution.
Cheng J, Wu C, Li J, Yang Q, Zhao M, Zhang X Nat Struct Mol Biol. 2025; .
PMID: 39789210 DOI: 10.1038/s41594-024-01454-9.
Bourgeois G, Coureux P, Lazennec-Schurdevin C, Madru C, Gaillard T, Duchateau M Nat Commun. 2025; 16(1):348.
PMID: 39753558 PMC: 11698992. DOI: 10.1038/s41467-024-55718-5.
Bhat S, Bhattacharya A, Li H, Cui X, Lueck J, Goldman Y bioRxiv. 2024; .
PMID: 39605609 PMC: 11601491. DOI: 10.1101/2024.11.13.623453.