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TitleN-methyladenosine in 5' UTR does not promote translation initiation.
Journal, issue, pagesMol Cell, Vol. 84, Issue 3, Page 584-595.e6, Year 2024
Publish dateFeb 1, 2024
AuthorsEwelina Guca / Rodrigo Alarcon / Michael Z Palo / Leonardo Santos / Santiago Alonso-Gil / Marcos Davyt / Leonardo H F de Lima / Fanny Boissier / Sarada Das / Bojan Zagrovic / Joseph D Puglisi / Yaser Hashem / Zoya Ignatova /
PubMed AbstractThe most abundant N-methyladenosine (mA) modification on mRNAs is installed non-stoichiometrically across transcripts, with 5' untranslated regions (5' UTRs) being the least conductive. 5' UTRs are ...The most abundant N-methyladenosine (mA) 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 mA remain poorly understood. Here, we combined structural, biochemical, and single-molecule approaches and show that at the most common position, a single mA 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 mA 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 mA interactions with the initiation complex and suggest that the subtle stabilization is unlikely to affect the translation dynamics under homeostatic conditions or stress.
External linksMol Cell / PubMed:38244546 / PubMed Central
MethodsEM (single particle)
Resolution3.04 - 3.3 Å
Structure data

17329

8p03

EMDB-17329, PDB-8p03:
48S late-stage initiation complex with m6A mRNA
Method: EM (single particle) / Resolution: 3.04 Å

17330

8p09

EMDB-17330, PDB-8p09:
48S late-stage initiation complex with non methylated mRNA
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-MG:
Unknown entry

Source
  • oryctolagus cuniculus (rabbit)
KeywordsTRANSLATION / translation initiation / ribosome / m6A / methylated mRNA / non methylated mRNA

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