期刊
MOLECULAR CELL
卷 68, 期 3, 页码 504-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2017.10.002
关键词
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资金
- US National Institutes of Health [R01AG042400]
- US Department of Defense [W81XWH-14-1-0068]
- HHMI Faculty Scholar [55108556]
In eukaryotic cells, protein synthesis typically begins with the binding of eIF4F to the 7-methylguanylate (m(7)G) 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 N-6-methyladenosine (m(6)A) 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 m(6)A-promoted translation under both stress and physiological conditions. Supporting the role of ABCF1 in m(6)A-facilitated mRNA translation, ABCF1-sensitive transcripts largely overlap with METTL3-dependent mRNA targets. By illustrating the scope and mechanism of eIF4F-independent mRNA translation, these findings reshape our current perceptions of cellular translational pathways.
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