ArticleNature communications2021
Somatic genetic rescue of a germline ribosome assembly defect.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 39 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 72 citations in OpenAlex.
- The Nucleolus in Human Disease: Ribosome Biogenesis, Nucleolar Surveillance, and Therapeutic Opportunities.Biomolecules · 2026Review
- Ribosome biogenesis and selective translational control as oncogenic vulnerabilities in hematologic malignancies.Molecular cancer · 2026Review
- Functional impact of the eIF6 N106S mutation on ribosome biogenesis in wild type and Shwachman-Diamond syndrome cells.Molecular medicine (Cambridge, Mass.) · 2026Article
- Insights in bone marrow failure syndromes: take home messages from the 3rd ESH-EBMT-EHA-IPIG translational research conference.Bone marrow transplantation · 2025Article
- The TP53 tumor suppressor gene: From molecular biology to clinical investigations.Journal of internal medicine · 2025Review
- Review
- Reduced EIF6 dosage attenuates TP53 activation in models of Shwachman-Diamond syndrome.The Journal of clinical investigation · 2025Article
- Selection for somatic escape variants in SERPINA1 in the liver of patients with alpha-1 antitrypsin deficiency.Nature genetics · 2025Article
- Sequestration of ribosomal subunits as inactive 80S by targeting eIF6 limits mitotic exit and cancer progression.Nucleic acids research · 2025Article
- Clonal landscape and clinical outcomes of telomere biology disorders: somatic rescue and cancer mutations.Blood · 2024Article
- From Challenge to Opportunity: How Shwachman-Diamond Syndrome Became a Promising Target for Therapy Development.Clinical pharmacology and therapeutics · 2024Article
- Update on Recommendations for Surveillance for Children with Predisposition to Hematopoietic Malignancy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- SURF2 is a MDM2 antagonist in triggering the nucleolar stress response.Nature communications · 2024Article
- Review
- Spontaneous remission and loss of monosomy 7: a window of opportunity for young children with SAMD9L syndrome.Haematologica · 2024Article
- The role of genetic factors in pediatric myelodysplastic syndromes with different outcomes.BMC pediatrics · 2024Article
- Clonal evolution in inherited marrow failure syndromes predicts disease progression.Hematology. American Society of Hematology. Education Program · 2023Review
- SBDSLife science alliance · 2023Article
- Germline predisposition traits in allogeneic hematopoietic stem-cell transplantation for myelodysplastic syndromes: a survey-based study and position paper on behalf of the Chronic Malignancies Working Party of the EBMT.The Lancet. Haematology · 2023Review
- Convergent somatic evolution commences in utero in a germline ribosomopathy.Nature communications · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
37 authors at 9 institutions in 7 countries.
Funding
Abstract
Indirect somatic genetic rescue (SGR) of a germline mutation is thought to be rare in inherited Mendelian disorders. Here, we establish that acquired mutations in the EIF6 gene are a frequent mechanism of SGR in Shwachman-Diamond syndrome (SDS), a leukemia predisposition disorder caused by a germline defect in ribosome assembly. Biallelic mutations in the SBDS or EFL1 genes in SDS impair release of the anti-association factor eIF6 from the 60S ribosomal subunit, a key step in the translational activation of ribosomes. Here, we identify diverse mosaic somatic genetic events (point mutations, interstitial deletion, reciprocal chromosomal translocation) in SDS hematopoietic cells that reduce eIF6 expression or disrupt its interaction with the 60S subunit, thereby conferring a selective advantage over non-modified cells. SDS-related somatic EIF6 missense mutations that reduce eIF6 dosage or eIF6 binding to the 60S subunit suppress the defects in ribosome assembly and protein synthesis across multiple SBDS-deficient species including yeast, Dictyostelium and Drosophila. Our data suggest that SGR is a universal phenomenon that may influence the clinical evolution of diverse Mendelian disorders and support eIF6 suppressor mimics as a therapeutic strategy in SDS.
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Registered trials
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.