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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/221285
Ribosomal protein deficiencies linked to Diamond-Blackfan anemia induce distinctive alterations of ATF4 expression
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Ribosomal protein haploinsufficiency causes Diamond-Blackfan anemia (DBA) and other ribosomopathies. DBA has been linked to p53 activation and reduced GATA1 expression, but these mechanisms do not fully explain the disease. This study unveils that deficiencies in small (RPS) or large (RPL) ribosomal subunit proteins cause a p53-independent loss of ATF4, a master regulator of stress responses and erythropoiesis, by reducing the pool of actively translating ATF4 mRNAs. This defect is more pronounced in RPS deficiencies because the loss of 40S, but not 60S, subunits cause a destabilization of ATF4 transcripts. ATF4 downregulation occurs in early hematopoietic progenitors and correlates with the severity of erythroid differentiation defects in patients with DBA. It is also linked to the de-repression of fetal hemoglobin in erythroid cells, a frequent feature in patients with DBA. Our findings indicate that impaired ATF4 expression might be a primary contributor to DBA and explain the aggravated erythroid failure of RPS-mutant patients.
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LORENZO MARTÍN, L. Francisco, et al. Ribosomal protein deficiencies linked to Diamond-Blackfan anemia induce distinctive alterations of ATF4 expression. iScience. 2025. Vol. 28, num. 4. ISSN 2589-0042. [consulted: 12 of August of 2026]. Available at: https://hdl.handle.net/2445/221285