Fig. 6: Reduced ribosomal stress attributes to the protective effect of glucocorticoids.

a Heatmap showing the scaled expression of key regulators and/or effectors associated with ribosomal transcription (MAX and TAF1C), ribosomal processing and transporter (NPM1 and XPO1) and translation initiator (EIF2B1, EIF2B2, EIF3A, and EIF4E) in C3 of all groups. b–d Line graphs showing the expression dynamics of total ribosomal protein genes (RPL + RPS), large ribosomal protein genes (RPL) and small ribosomal protein genes (RPS) in all (b), RPL mutant (c) and RPS mutant (d) samples across clusters. Different donor types are coded with the indicated color. e A hypothetical model illustrating altered biological processes that lead to cellular distress and pathogenesis of DBA (upper). The imbalance between the innate fast cell cycle and insufficient protein biosynthesis, which results from RP mutation, could trigger DNA replication stress in the BFU-E cells of DBA patients; and concomitantly elicit DNA damage-induced P53 activation and apoptosis. The lower panel shows a proposed schematic of the therapeutic mechanism of GCs. GC administration elevates IFN signaling, which attenuates cell proliferation by regulating the activity of cell cycle regulators and modulators (e.g., MYC, CDK4, and CDK6). It also alleviates ribosomal stress via the repression of MYC, thereby rectifying the imbalance and ultimately ameliorating apoptosis and promoting cell survival.