2. Academic Validation
  3. 5' UTR m(6)A Promotes Cap-Independent Translation

5' UTR m(6)A Promotes Cap-Independent Translation

  • Cell. 2015 Nov 5;163(4):999-1010. doi: 10.1016/j.cell.2015.10.012.
Kate D Meyer 1,  Deepak P Patil 1,  Jun Zhou 2,  Alexandra Zinoviev 3,  Maxim A Skabkin 3,  Olivier Elemento 4,  Tatyana V Pestova 3,  Shu-Bing Qian 2,  Samie R Jaffrey 5
Affiliations

Affiliations

  • 1 Department of Pharmacology, Weill Medical College, Cornell University, New York, NY 10065, USA.
  • 2 Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
  • 3 Department of Cell Biology, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
  • 4 Department of Physiology and Biophysics, Weill Medical College, Cornell University, New York, NY 10065, USA; HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Medical College, Cornell University, New York, NY 10065, USA.
  • 5 Department of Pharmacology, Weill Medical College, Cornell University, New York, NY 10065, USA. Electronic address: [email protected].
PMID: 26593424 DOI: 10.1016/j.cell.2015.10.012
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.

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