eIF3d specialized translation requires a RACK1-driven eIF3d binding to 43S PIC in proliferating SH-SY5Y neuroblastoma cells

Translation initiation of most mammalian mRNAs is mediated by a 5′ cap structure that binds eukaryotic initiation factor 4E (eIF4E). Notably, most mRNAs are still capped when eIF4E is inhibited, suggesting alternative mechanisms likely mediate cap-dependent mRNA translation without functional eIF4F. Here we found that, when eIF4E is inhibited, the ribosomal scaffold RACK1 recruits eIF3d on the 43S pre-initiation complex. Moreover, we found that it is just PKCBII in its active form that promotes the binding of RACK1 to eIF3d. These studies disclose a previously unknown role of ribosomal RACK1 for eIF3d specialized translation. •eIF3d requires RACK1 for the binding to translational machinery and its activity.•The binding of eIF3d with ribosomal RACK1 is required for the cyclin D2 expression.•The PKCβII modulates the eIF3d-RACK1 binding.•The eIF3d-RACK1 complex is active in mTORC1 blocking conditions.•The eIF3d-RACK1 complex controls the HSP-70 mRNA translation.