5′ UTR m6A promotes cap-independent translation
Cell, 2015•cell.com
Protein translation typically begins with the recruitment of the 43S ribosomal complex to the
5′ cap of mRNAs by a cap-binding complex. However, some transcripts are translated in a
cap-independent manner through poorly understood mechanisms. Here, we show that
mRNAs containing N 6-methyladenosine (m 6 A) in their 5′ UTR can be translated in a cap-
independent manner. A single 5′ UTR m 6 A directly binds eukaryotic initiation factor 3
(eIF3), which is sufficient to recruit the 43S complex to initiate translation in the absence of …
5′ cap of mRNAs by a cap-binding complex. However, some transcripts are translated in a
cap-independent manner through poorly understood mechanisms. Here, we show that
mRNAs containing N 6-methyladenosine (m 6 A) in their 5′ UTR can be translated in a cap-
independent manner. A single 5′ UTR m 6 A directly binds eukaryotic initiation factor 3
(eIF3), which is sufficient to recruit the 43S complex to initiate translation in the absence of …
Summary
Protein translation typically begins with the recruitment of the 43S ribosomal complex to the 5′ cap of mRNAs by a cap-binding complex. However, some transcripts are translated in a cap-independent manner through poorly understood mechanisms. Here, we show that mRNAs containing N6-methyladenosine (m6A) in their 5′ UTR can be translated in a cap-independent manner. A single 5′ UTR m6A directly binds eukaryotic initiation factor 3 (eIF3), which is sufficient to recruit the 43S complex to initiate translation in the absence of the cap-binding factor eIF4E. Inhibition of adenosine methylation selectively reduces translation of mRNAs containing 5′UTR m6A. Additionally, increased m6A levels in the Hsp70 mRNA regulate its cap-independent translation following heat shock. Notably, we find that diverse cellular stresses induce a transcriptome-wide redistribution of m6A, resulting in increased numbers of mRNAs with 5′ UTR m6A. These data show that 5′ UTR m6A bypasses 5′ cap-binding proteins to promote translation under stresses.
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