OpenLab

A number of ribosomal proteins seem to be involved in Diamond-Blackfan anemia 1. While the crystal structure of ribosome (such as 3J7R) indicate no interaction between them, and rather interaction with 18S rRNA, it seems like the problem lies at the level of ribosome assembly and maturation of rRNA.

Using small interfering RNA (siRNA), Flygare et al. (2007) showed that reduced expression of RPS19 in a human erythroleukemia cell line led to a defect in maturation of the 40S ribosomal subunits, affected erythroid differentiation, and increased apoptosis. Cells expressing siRNA targeting RPS19 failed to efficiently cleave 21S pre-rRNAs at the E site within internal transcribed sequence-1, which would normally lead to formation of the mature 3-prime end of the 18S rRNA. CD34 (142230)-negative and CD34-positive bone marrow cells from DBA patients with mutations in RPS19 showed an increased ratio of 21S to 18SE pre-rRNA compared with healthy controls, and the defect was more pronounced in CD34-negative patient cells. The findings indicated that RPS19 is required for efficient maturation of 40S ribosomal subunits. The results showed that cells from patients with DFA have a defect in pre-rRNA processing, and Flygare et al. (2007) concluded that the disorder results from defects in ribosome synthesis.

Source: OMIM Entry – # 105650 – DIAMOND-BLACKFAN ANEMIA 1; DBA1

How these translate into problem with erythrogenesis only?