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

Published

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 2015

Published In

Volume / Issue

  • 163 / 4

Start / End Page

  • 999 - 1010

PubMed ID

  • 26593424

Pubmed Central ID

  • 26593424

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2015.10.012

Language

  • eng