TRIBE editing reveals specific mRNA targets of eIF4E-BP in Drosophila and in mammals

  • Sci Adv. 2020 Aug 12;6(33):eabb8771. doi: 10.1126/sciadv.abb8771.
Hua Jin  1  2 ,  Weijin Xu  1 ,  Reazur Rahman  1 ,  Daxiang Na  1 ,  Allegra Fieldsend  1 ,  Wei Song  2 ,  Shaobo Liu  2 ,  Chong Li  2 ,  Michael Rosbash  1
Affiliations
  • 1. Department of Biology, Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02453, USA.
  • 2. Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, No. 5 South Zhongguancun Street, Beijing 100081, People's Republic of China.
PMID: 32851185 DOI: 10.1126/sciadv.abb8771
Abstract

4E-BP (eIF4E-BP) represses translation initiation by binding to the 5' cap-binding protein eIF4E and inhibiting its activity. Although 4E-BP has been shown to be important in growth control, stress response, Cancer, neuronal activity, and mammalian circadian rhythms, it is not understood how it preferentially represses a subset of mRNAs. We successfully used HyperTRIBE (targets of RNA binding proteins identified by editing) to identify in vivo 4E-BP mRNA targets in both Drosophila and mammals under conditions known to activate 4E-BP. The protein associates with specific mRNAs, and ribosome profiling data show that mTOR inhibition changes the translational efficiency of 4E-BP TRIBE targets more substantially compared to nontargets. In both systems, these targets have specific motifs and are enriched in translation-related pathways, which correlate well with the known activity of 4E-BP and suggest that it modulates the binding specificity of eIF4E and contributes to mTOR translational specificity.

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