Title | 5' UTR m(6)A Promotes Cap-Independent Translation. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Meyer KD, Patil DP, Zhou J, Zinoviev A, Skabkin MA, Elemento O, Pestova TV, Qian S-B, Jaffrey SR |
Journal | Cell |
Volume | 163 |
Issue | 4 |
Pagination | 999-1010 |
Date Published | 2015 Nov 05 |
ISSN | 1097-4172 |
Keywords | 5' Untranslated Regions, Adenosine, Animals, Embryo, Mammalian, Eukaryotic Initiation Factor-3, Eukaryotic Initiation Factor-4E, Fibroblasts, HeLa Cells, HSP72 Heat-Shock Proteins, Humans, Mice, Peptide Chain Initiation, Translational, Protein Biosynthesis, Ribosomes |
Abstract | 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. |
DOI | 10.1016/j.cell.2015.10.012 |
Alternate Journal | Cell |
PubMed ID | 26593424 |
PubMed Central ID | PMC4695625 |
Grant List | R01 GM059660 / GM / NIGMS NIH HHS / United States T32 CA062948 / CA / NCI NIH HHS / United States K99MH104712 / MH / NIMH NIH HHS / United States R01 CA186702 / CA / NCI NIH HHS / United States R01 AG042400 / AG / NIA NIH HHS / United States K99 MH104712 / MH / NIMH NIH HHS / United States R01DA037755 / DA / NIDA NIH HHS / United States GM59660 / GM / NIGMS NIH HHS / United States AG042400 / AG / NIA NIH HHS / United States R01 DA037755 / DA / NIDA NIH HHS / United States |