Turning up the HEAT(R3) in Diamond-Blackfan anemia.

Abstract

In this issue of Blood, O’Donohue et al1 identify biallelic mutations in HEATR3 as the underpinning cause of Diamond-Blackfan anemia (DBA) in 4 unrelated pedigrees. By using primary human cells, cell lines, and yeast models with HEATR3 deficiency, they delineate a mechanism by which reduced HEATR3 leads to erythroid failure. The mechanism includes impaired nuclear import of ribosomal protein uL18 (encoded by RPL5), defects in ribosomal RNA processing, and reduced production of the large (60S) ribosomal subunit, leading to p53-independent perturbation of erythroid development.