Association and interactions of the RIO kinases in the context of Diamond-Blackfan anemia

Diamond-Blackfan anemia (DBA) is a rare and phenotypically variable inherited bone marrow failure syndrome caused by mutations in RPS and RPL genes and thus generally considered a ribosomopathy. Main symptome is a maturation block during erythropoiesis, a process tightly regulated by transcription factors such as GATA1. We recently identified a RIOK1 duplication in a DBA patient who did not have a RPS/RPL mutation. RIOK (right open frame kinase) proteins (i.e. RIOK1, RIOK2, RIOK3) play a plethora of roles, especially in the maturation of the 40S subunit of ribosomes. RIOK2 was recently described to play a major role in haematopoiesis by affecting transcription factors like GATA1/2, SPI1, RUNX3 and KLF1. We are investigating whether also RIOK1 is involved in haematopoiesis. We showed that RIOK1 overexpression resulted in a rapid loss of hematopoietic stem and progenitor cells and a reduced propensity to differentiate towards red blood cells. We conclude that RIOK1 is a novel DBA-associated gene and are currently investigating whether and how RIOK1 and RIOK2 cooperate during hematopoiesis.