The daily production of up to 1011 erythrocytes is tightly controlled to maintain the number of erythrocytes in peripheral blood between narrow boundaries. Availability of growth factors and nutrients, particularly iron, control the proliferation and survival of precursor cells partly through control of mRNA translation. General translation initiation mechanisms can selectively control translation of transcripts that carry specific structures in the UTRs. This selective mRNA translation is an important layer of gene expression regulation in erythropoiesis. Ribosome profiling is a recently developed high throughput sequencing technique for global mapping of translation initiation sites across the transcriptome. Here we describe what is known about control of mRNA translation in erythropoiesis and how ribosome profiling will help to further our knowledge. Ribosome footprinting will give insight in transcript-specific translation at codon resolution, which is of great value to understand many cellular processes during erythropoiesis. It will be of particular interest to understand responses to iron availability and reactive oxygen species (ROS), which affects translation initiation of transcripts harbouring upstream ORFs (uORF) and potential alternative downstream ORFs (aORF).

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