Diamond-Blackfan anemia (DBA) is a rare bone marrow failure disorder primarily caused by mutations in ribosomal proteins (RPs), including RPS24, leading to impaired erythropoiesis. Despite advances in our understanding of the roles of other RPs, the mechanisms underlying RPS24-related DBA remain unclear. Therefore, in this study, we aimed to investigate the effect of RPS24 haploinsufficiency on erythropoiesis using a zebrafish model. RPS24 knockdown via morpholino injection significantly reduced the hemoglobin levels, as confirmed by O-dianisidine staining and whole-mount in situ hybridization. Further analysis revealed that RPS24 deficiency downregulated the expression of SATB homeobox 1a (satb1a), a key regulator of erythroid differentiation, by inhibiting the signal transducer and activator of transcription 6 (STAT6) signaling pathway. Western blotting analysis revealed decreased levels of pSTAT6 correlated with the decrease in downstream erythroid marker levels. satb1a knockdown further impaired erythropoiesis in zebrafish, reinforcing its critical role in DBA pathogenesis. Overall, our findings suggest that RPS24 haploinsufficiency leads to DBA by disrupting the STAT6-SATB1 axis, providing novel insights into the molecular mechanisms underlying erythropoietic failure in DBA. Furthermore, this study highlights the importance of zebrafish models for further exploration of therapeutic targets for DBA.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbrc.2025.151563 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
RPS24 haploinsufficiency impairs erythropoiesis in the Diamond-Blackfan anemia zebrafish model via the STAT6-SATB1 pathway.
Biochem Biophys Res Commun
March 2025
Department of Biochemistry, School of Medicine, Pusan National University, Yangsan, 50612, South Korea. Electronic address:
Diamond-Blackfan anemia (DBA) is a rare bone marrow failure disorder primarily caused by mutations in ribosomal proteins (RPs), including RPS24, leading to impaired erythropoiesis. Despite advances in our understanding of the roles of other RPs, the mechanisms underlying RPS24-related DBA remain unclear. Therefore, in this study, we aimed to investigate the effect of RPS24 haploinsufficiency on erythropoiesis using a zebrafish model.
View Article and Find Full Text PDFDifferential expression of ribosomal proteins in myelodysplastic syndromes.
J Clin Pathol
February 2016
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Aberrations of ribosomal biogenesis have been implicated in several congenital bone marrow failure syndromes, such as Diamond-Blackfan anaemia, Shwachman-Diamond syndrome and Dyskeratosis Congenita. Recent studies have identified haploinsufficiency of RPS14 in the acquired bone marrow disease isolated 5q minus syndrome, a subtype of myelodysplastic syndromes (MDS). However, the expression of various proteins comprising the ribosomal subunits and other proteins enzymatically involved in the synthesis of the ribosome has not been explored in non-5q minus MDS.
View Article and Find Full Text PDFRibosomal protein mutations in Korean patients with Diamond-Blackfan anemia.
Exp Mol Med
March 2014
Department of Laboratory Medicine, College of Medicine, Chosun University, Gwangju, Korea.
Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by hypoproliferative anemia, associated physical malformations and a predisposition to cancer. DBA has been associated with mutations and deletions in the large and small ribosomal protein genes, and genetic aberrations have been detected in ∼50-60% of patients. In this study, nine Korean DBA patients were screened for mutations in eight known DBA genes (RPS19, RPS24, RPS17, RPS10, RPS26, RPL35A, RPL5 and RPL11) using the direct sequencing method.
View Article and Find Full Text PDFFibroblasts from patients with Diamond-Blackfan anaemia show abnormal expression of genes involved in protein synthesis, amino acid metabolism and cancer.
BMC Genomics
September 2009
Department of Medical Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy.
Article Synopsis
- Diamond-Blackfan anaemia (DBA) is a rare inherited condition affecting red blood cell production, linked to mutations in various ribosomal protein genes and an increased risk of solid tumors.
- Research shows that DBA patients have altered gene expression in fibroblasts, with 421 differentially expressed genes identified, impacting ribosomal proteins, protein synthesis, and factors related to cell death and development.
- This study highlights the involvement of non-blood cell types in DBA, suggesting that defects in protein synthesis may contribute to the condition's pathology.
Abnormalities of the large ribosomal subunit protein, Rpl35a, in Diamond-Blackfan anemia.
Blood
September 2008
Division of Pediatric Oncology, Department of Oncology, Kimmel Comprehensive Cancer Center.
Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by anemia, congenital abnormalities, and cancer predisposition. Small ribosomal subunit genes RPS19, RPS24, and RPS17 are mutated in approximately one-third of patients. We used a candidate gene strategy combining high-resolution genomic mapping and gene expression microarray in the analysis of 2 DBA patients with chromosome 3q deletions to identify RPL35A as a potential DBA gene.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!