M⁶A Facilitates eIF4F-Independent mRNA Translation.

ABSTRACT: In eukaryotic cells, protein synthesis typically begins with the binding of eIF4F to the 7-methylguanylate (m⁷G) cap found on the 5' end of the majority of mRNAs. Surprisingly, overall translational output remains robust under eIF4F inhibition. The broad spectrum of eIF4F-resistant translatomes is incompatible with cap-independent translation mediated by internal ribosome entry sites (IRESs). Here, we report that N⁶-methyladenosine (m⁶A) facilitates mRNA translation that is resistant to eIF4F inactivation. Depletion of the methyltransferase METTL3 selectively inhibits translation of mRNAs bearing 5' UTR methylation, but not mRNAs with 5' terminal oligopyrimidine (TOP) elements. We identify ABCF1 as a critical mediator of m⁶A-promoted translation

SUBMITTER: Coots RA 

PROVIDER: S-EPMC5913006 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature