7UCJ

Mammalian 80S translation initiation complex with mRNA and Harringtonine

This is a non-PDB format compatible entry.

Summary for 7UCJ

• Entry DOI: 10.2210/pdb7ucj/pdb
• EMDB information: 26444 26445
• Descriptor: P-site tRNA, Ribosomal_L18_c domain-containing protein, 60S ribosomal protein L6, ... (82 entities in total)
• Functional Keywords: mammalian, 80s, initiation, complex, mrna modification, harringtonine, ribosome-inhibitor complex, ribosome/inhibitor
• Biological source: Oryctolagus cuniculus (rabbit); More
• Total number of polymer chains: 79
• Total formula weight: 3094043.69

Authors

Yang, R.,Arango, D.,Sturgill, D.,Oberdoerffer, S. (deposition date: 2022-03-16, release date: 2022-06-01, Last modification date: 2022-08-17)

Primary citation

Arango, D.,Sturgill, D.,Yang, R.,Kanai, T.,Bauer, P.,Roy, J.,Wang, Z.,Hosogane, M.,Schiffers, S.,Oberdoerffer, S.
Direct epitranscriptomic regulation of mammalian translation initiation through N4-acetylcytidine.
Mol.Cell, 82:2797-2814.e11, 2022

PubMed Abstract: mRNA function is influenced by modifications that modulate canonical nucleobase behavior. We show that a single modification mediates distinct impacts on mRNA translation in a position-dependent manner. Although cytidine acetylation (ac4C) within protein-coding sequences stimulates translation, ac4C within 5' UTRs impacts protein synthesis at the level of initiation. 5' UTR acetylation promotes initiation at upstream sequences, competitively inhibiting annotated start codons. Acetylation further directly impedes initiation at optimal AUG contexts: ac4C within AUG-flanking Kozak sequences reduced initiation in base-resolved transcriptome-wide HeLa results and in vitro utilizing substrates with site-specific ac4C incorporation. Cryo-EM of mammalian 80S initiation complexes revealed that ac4C in the -1 position adjacent to an AUG start codon disrupts an interaction between C and hypermodified t6A at nucleotide 37 of the initiator tRNA. These findings demonstrate the impact of RNA modifications on nucleobase function at a molecular level and introduce mRNA acetylation as a factor regulating translation in a location-specific manner.

PubMed: 35679869
DOI: 10.1016/j.molcel.2022.05.016

Experimental method

ELECTRON MICROSCOPY (3.1 Å)