Figure 1. Hypothetical features of the translational readout hypothesis for DBA pathophysiology.

Left panel, proteins translated when subunit synthesis is balanced. Proteins labeled in red show a severe reduction in synthesis under conditions of increased mRNA competition for translation when either subunit level is decreased (middle and right panel). Middle panel, decreased 40S production. The general reduction in protein synthesis brought about by reduced amounts of 40S subunits is shown by dashed grey lines. Translation of some mRNAs (TOP mRNAs) is specifically enhanced when 40S subunit production is reduced. Proteins in red in left panel are severely reduced in amount when 40S subunits are depleted. Right panel, decreased 60S subunit production. It is expected that the translation of certain mRNA may be preferentially affected by the subunit affected. Here certain proteins with enhanced expression when 40S subunits are depleted show reduced expression when 60S subunits are depleted. Other proteins may exhibit enhanced expression when 60S subunits are depleted relative to 40S subunit depletion. Finally, mRNAs for proteins shown in red in the left panel may be preferentially affected by reduced amounts 60S as well as 40S subunits. These proteins could be of interest as critical factors responsible for generic features of DBA common to haploinsufficiency for proteins of either ribosomal subunit.