Jin, H., Xu, W., Rahman, R., Na, D., Fieldsend, A., Song, W., Liu, S., Li, C., Rosbash, M. (2020). TRIBE editing reveals specific mRNA targets of eIF4E-BP in Drosophila and in mammals.  Sci. Adv. 6(33): eabb8771.

FBrf0246552

Research paper

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.

PMC7423359 (PMC) (EuropePMC)