Widespread and Dynamic Translational Control of Red Blood Cell Development

Cell development requires tight yet dynamic control of protein production. Here, we use murine erythropoiesis as a model to study translational regulatory dynamics during mammalian cell differentiation. We uncover pervasive translational control of protein synthesis, including widespread alternative translation initiation and termination, stoichiometric synthesis, and dynamic use of upstream reading frames. In addition, we identify hundreds of mRNAs with dynamic translation efficiencies during erythropoiesis. Interestingly, these mRNAs have significantly enriched binding motifs of many mRNA-binding proteins that are expressed with high specificity in hematopoietic cells, suggesting that those mRNA-binding proteins are important players in the translational regulatory programs in erythropoiesis. A major such program involves enhanced decoding of specific mRNAs depleted in terminally differentiating/enucleating cells with decreasing transcriptional capacity. We functionally characterized one such protein, Rbm38, which was previously identified as a splicing factor in terminal erythropoiesis, can enhance the translation of a subset of those mRNAs by interacting with the general translation initiation factor eIF4G in erythroid cells. Altogether, our findings reveal widespread and dynamic translational control in supporting specialized mammalian cell formation.