5' UTR m(6)A Promotes Cap-Independent Translation.
Journal Article (Journal Article)
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 the cap-binding factor eIF4E. Inhibition of adenosine methylation selectively reduces translation of mRNAs containing 5'UTR m(6)A. Additionally, increased m(6)A 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 m(6)A, resulting in increased numbers of mRNAs with 5' UTR m(6)A. These data show that 5' UTR m(6)A bypasses 5' cap-binding proteins to promote translation under stresses.
Full Text
Duke Authors
Cited Authors
- Meyer, KD; Patil, DP; Zhou, J; Zinoviev, A; Skabkin, MA; Elemento, O; Pestova, TV; Qian, S-B; Jaffrey, SR
Published Date
- November 5, 2015
Published In
Volume / Issue
- 163 / 4
Start / End Page
- 999 - 1010
PubMed ID
- 26593424
Pubmed Central ID
- PMC4695625
Electronic International Standard Serial Number (EISSN)
- 1097-4172
Digital Object Identifier (DOI)
- 10.1016/j.cell.2015.10.012
Language
- eng
Conference Location
- United States