ArticleBlood2015
Ott1 (Rbm15) regulates thrombopoietin response in hematopoietic stem cells through alternative splicing of c-Mpl.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 51 citations in OpenAlex.
- RBM15 in leukemogenesis: an emerging regulator at the interface of RNA biology and hematopoiesis.Trends in cancer · 2026Review
- Imbalance of c-MPL Isoform Promotes Tumorigenesis by Activating STAT-5 in Leukemic Cell Lines.Current issues in molecular biology · 2026Article
- Thrombopoietin Receptor MPL in Hematopoiesis and Myeloproliferative Neoplasms: Physiological Roles and Pathogenic Mechanisms.Stem cell reviews and reports · 2026Review
- RBM15 in diseases: Molecular mechanisms and clinical opportunities from RNA mGenes & diseases · 2026Review
- NNature reviews. Cancer · 2026Review
- RBFOX2-dependent alternative splicing of Numb regulates Notch signaling during muscle stem cell activation.Stem cell reports · 2026Article
- Article
- RBM15-mediated the m6A modification of MAT2A promotes osteosarcoma cell proliferation, metastasis and suppresses ferroptosis.Molecular and cellular biochemistry · 2025Article
- RNA Binding Motif Protein 15 (RBM15): Structure, Function and Its Research Progress in Tumors.International journal of general medicine · 2025Review
- Cellular stress and epigenetic regulation in adult stem cells.Life science alliance · 2024Review
- A review on the functional characteristics of the c-Myeloproliferative Leukaemia (c-MPL) gene and its isoforms.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Epigenetic regulation of megakaryopoiesis and platelet formation.Haematologica · 2024Review
- Review
- RBM15 Protects From Myocardial Infarction by Stabilizing NAE1.JACC. Basic to translational science · 2024Article
- Exploring the role of mFrontiers in oncology · 2024Review
- Identification of region-specific splicing QTLs in human hippocampal tissue and its distinctive role in brain disorders.iScience · 2023Article
- Melanocortin/MC5R axis regulates the proliferation of hematopoietic stem cells in mice after ionizing radiation injury.Blood advances · 2023Article
- Regulation of adult stem cell quiescence and its functions in the maintenance of tissue integrity.Nature reviews. Molecular cell biology · 2023Review
- SPOC domain proteins in health and disease.Genes & development · 2023Review
- RBM15 suppresses hepatic insulin sensitivity of offspring of gestational diabetes mellitus mice via m6A-mediated regulation of CLDN4.Molecular medicine (Cambridge, Mass.) · 2023Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Thrombopoietin (Thpo) signaling through the c-Mpl receptor promotes either quiescence or proliferation of hematopoietic stem cells (HSCs) in a concentration-dependent manner; however, in vivo Thpo serum levels are responsive to platelet mass rather than HSC demands, suggesting additional regulation exists. Ott1 (Rbm15), a spliceosomal component originally identified as a fusion partner in t(1;22)-associated acute megakaryocytic leukemia, is also essential for maintaining HSC quiescence under stress. Ott1 controls the alternative splicing of a dominant negative isoform, Mpl-TR, capable of inhibiting HSC engraftment and attenuating Thpo signaling. Ott1, which associates with Hdac3 and the histone methyltransferase, Setd1b, binds to both c-Mpl RNA and chromatin and regulates H4 acetylation and H3K4me3 marks. Histone deacetylase or histone methyltransferase inhibition also increases Mpl-TR levels, suggesting that Ott1 uses an underlying epigenetic mechanism to control alternative splicing of c-Mpl. Manipulation of Ott1-dependent alternative splicing may therefore provide a novel pharmacologic avenue for regulating HSC quiescence and proliferation in response to Thpo.
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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.