Regulation of ribosome recycling in platelets and reticulocytes
Mills, Eric William
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During red blood cell (RBC) and platelet formation in mammals, translation proceeds in the absence of new mRNA synthesis. The mechanisms of translational control operating during these phases of non-nucleated blood cell terminal differentiation are incompletely understood. Here, we comprehensively profiled translation by maturing RBCs and platelets using ribosome profiling, expanding the role that should be anticipated for translation and its control in these cell types. Next, using in vitro models of erythroid and megakaryoid differentiation, we present evidence supporting a differentiation-dependent switch in the machinery responsible for dissociating (“recycling”) ribosomes from mRNAs after translation termination. This switch involves the loss of ABCE1-mediated ribosome recycling, which is compensated by upregulation of PELO/HBS1L. We demonstrate, in the early phases of differentiation of K562 cells, that PELO/HBS1L induction promotes hemoglobin synthesis at the translational level by increasing the availability ribosomes. In the latest phase of differentiation, we show that there is a nearly complete loss of ribosome recycling factors leading the dramatic increase in occupancy of 3 ́UTRs by ribosomes.