5′ UTR m6A Promotes Cap-Independent Translation
| Autor: | Maxim A. Skabkin, Jun Zhou, Tatyana V. Pestova, Alexandra Zinoviev, Shu-Bing Qian, Samie R. Jaffrey, Olivier Elemento, Deepak P. Patil, Kate D. Meyer |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Untranslated region
Adenosine Five prime untranslated region Eukaryotic Initiation Factor-3 HSP72 Heat-Shock Proteins Biology General Biochemistry Genetics and Molecular Biology Article Mice Eukaryotic translation Eukaryotic initiation factor Initiation factor Animals Humans Peptide Chain Initiation Translational Biochemistry Genetics and Molecular Biology(all) EIF4E Rotavirus translation Fibroblasts Embryo Mammalian Molecular biology Eukaryotic translation initiation factor 4 gamma Eukaryotic Initiation Factor-4E Protein Biosynthesis 5' Untranslated Regions Ribosomes HeLa Cells |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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