7UCK

80S translation initiation complex with ac4c(-1) mRNA and Harringtonine

これはPDB形式変換不可エントリーです。

7UCK の概要

• エントリーDOI: 10.2210/pdb7uck/pdb
• EMDBエントリー: 26444 26445
• 分子名称: P-site tRNA, Ribosomal_L18_c domain-containing protein, 60S ribosomal protein L6, ... (82 entities in total)
• 機能のキーワード: mammalian, 80s, initiation, complex, mrna modification, mrna acetylation, harringtonine, ribosome-inhibitor complex, ribosome/inhibitor
• 由来する生物種: Oryctolagus cuniculus (rabbit); 詳細
• タンパク質・核酸の鎖数: 79
• 化学式量合計: 3113436.44

構造登録者

Yang, R.,Arango, D.,Sturgill, D.,Oberdoerffer, S. (登録日: 2022-03-16, 公開日: 2022-06-01, 最終更新日: 2024-12-25)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (2.8 Å)