DSSR-PyMOL cartoon-block schematics: PDB entry 8p03

PDB-id

8p03; DSSR-derived features in text and JSON formats

Class

translation

Method

cryo-EM (3.04 Å)

Summary

48s late-stage initiation complex with m6a mrna

Reference

Guca E, Alarcon R, Palo MZ, Santos L, Alonso-Gil S, Davyt M, de Lima LHF, Boissier F, Das S, Zagrovic B, Puglisi JD, Hashem Y, Ignatova Z (2024): "N 6 -methyladenosine in 5' UTR does not promote translation initiation." Mol.Cell, 84, 584-595.e6. doi: 10.1016/j.molcel.2023.12.028.

Abstract

The most abundant N₆-methyladenosine (m₆A) modification on mRNAs is installed non-stoichiometrically across transcripts, with 5' untranslated regions (5' UTRs) being the least conductive. 5' UTRs are essential for translation initiation, yet the molecular mechanisms orchestrated by m₆A remain poorly understood. Here, we combined structural, biochemical, and single-molecule approaches and show that at the most common position, a single m₆A does not affect translation yields, the kinetics of translation initiation complex assembly, or start codon recognition both under permissive growth and following exposure to oxidative stress. Cryoelectron microscopy (cryo-EM) structures of the late preinitiation complex reveal that m₆A purine ring established stacking interactions with an arginine side chain of the initiation factor eIF2α, although with only a marginal energy contribution, as estimated computationally. These findings provide molecular insights into m₆A interactions with the initiation complex and suggest that the subtle stabilization is unlikely to affect the translation dynamics under homeostatic conditions or stress.