Diamond-Blackfan anemia (DBA) typically presents with red blood cell aplasia 
that usually manifests in the first year of life. The only gene currently known 
to be mutated in DBA encodes ribosomal protein S19 (RPS19). Previous studies 
have shown that the yeast RPS19 protein is required for a specific step in the 
maturation of 40S ribosomal subunits. Our objective here was to determine 
whether the human RPS19 protein functions at a similar step in 40S subunit 
maturation. Studies where RPS19 expression is reduced by siRNA in the 
hematopoietic cell line, TF-1, show that human RPS19 is also required for a 
specific step in the maturation of 40S ribosomal subunits. This maturation 
defect can be monitored by studying rRNA-processing intermediates along the 
ribosome synthesis pathway. Analysis of these intermediates in CD34- cells from 
the bone marrow of patients with DBA harboring mutations in RPS19 revealed a 
pre-rRNA-processing defect similar to that observed in TF-1 cells where RPS19 
expression was reduced. This defect was observed to a lesser extent in CD34+ 
cells from patients with DBA who have mutations in RPS19.