ArticleBlood2022
HEATR3 variants impair nuclear import of uL18 (RPL5) and drive Diamond-Blackfan anemia.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 37 citations in OpenAlex.
- Illuminating ribosome biogenesis disorders through structural biology.RNA biology · 2026Review
- The Nucleolus in Human Disease: Ribosome Biogenesis, Nucleolar Surveillance, and Therapeutic Opportunities.Biomolecules · 2026Review
- Convergent nuclear proteostasis alterations across 40S ribosomal protein deficiencies.Nature communications · 2026Article
- Ribosomal RNA processing impairments in a B cell immunodeficient patient with WDR75 variants.Journal of human immunity · 2026Article
- Article
- Functional impact of a deep intronic variant in the RPS19 gene detected in a case of Diamond-Blackfan anemia syndrome.Haematologica · 2026Article
- Article
- Imaging-mediated genetic effects link brain microstructure, metabolic profiles, and regional transcription to glioma susceptibility.Frontiers in immunology · 2026Article
- RPL5 deficiency-induced ribosomal stress targets a select subset of proteins and inhibits the PI3K-Akt-mTOR signaling pathway to eradicate leukemia stem cells.Cell death & disease · 2025Article
- Multi-omics Analysis Implicates Mitochondrial Complex Assembly Protein COX18 in Mitochondrial Signaling and Tumorigenesis across Cancers.Cell biochemistry and biophysics · 2025Article
- Review
- Review
- A novel mouse model to study the effects of new therapies for Diamond-Blackfan anemia.Blood advances · 2025Article
- Biallelic variants in the conserved ribosomal protein chaperone geneProceedings of the National Academy of Sciences of the United States of America · 2025Article
- HEATR3 recognizes membrane rupture and facilitates xenophagy in response toProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Regulated GATA1 expression as a universal gene therapy for Diamond-Blackfan anemia.Cell stem cell · 2025Article
- Case Report: Clinical management of a severe DBA patient with a novel RPS19 mutation.Frontiers in pediatrics · 2025Article
- SURF2 is a MDM2 antagonist in triggering the nucleolar stress response.Nature communications · 2024Article
- Reovirus infection induces transcriptome-wide unique A-to-I editing changes in the murine fibroblasts.Virus research · 2024Article
- Base Editors-Mediated Gene Therapy in Hematopoietic Stem Cells for Hematologic Diseases.Stem cell reviews and reports · 2024Review
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Authors and funding
28 authors at 11 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The congenital bone marrow failure syndrome Diamond-Blackfan anemia (DBA) is typically associated with variants in ribosomal protein (RP) genes impairing erythroid cell development. Here we report multiple individuals with biallelic HEATR3 variants exhibiting bone marrow failure, short stature, facial and acromelic dysmorphic features, and intellectual disability. These variants destabilize a protein whose yeast homolog is known to synchronize the nuclear import of RPs uL5 (RPL11) and uL18 (RPL5), which are both critical for producing ribosomal subunits and for stabilizing the p53 tumor suppressor when ribosome biogenesis is compromised. Expression of HEATR3 variants or repression of HEATR3 expression in primary cells, cell lines of various origins, and yeast models impairs growth, differentiation, pre-ribosomal RNA processing, and ribosomal subunit formation reminiscent of DBA models of large subunit RP gene variants. Consistent with a role of HEATR3 in RP import, HEATR3-depleted cells or patient-derived fibroblasts display reduced nuclear accumulation of uL18. Hematopoietic progenitor cells expressing HEATR3 variants or small-hairpin RNAs knocking down HEATR3 synthesis reveal abnormal acceleration of erythrocyte maturation coupled to severe proliferation defects that are independent of p53 activation. Our study uncovers a new pathophysiological mechanism leading to DBA driven by biallelic HEATR3 variants and the destabilization of a nuclear import protein important for ribosome biogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.