ArticleGenome biology2024
RNA-binding protein RBM5 plays an essential role in acute myeloid leukemia by activating the oncogenic protein HOXA9.
Article in Genome biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 7 citations in OpenAlex.
- RBM protein family: Focusing on the occurrence, progression and treatment of cancer.Medical oncology (Northwood, London, England) · 2026Review
- Article
- A Real-Data-Driven Framework for Evaluating Differential Transcript Usage Methods Across Long-Read Bulk, Single-Cell, and Spatial Transcriptomics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PTBP1 controls oncogenic transcript processing and maintenance of acute myeloid leukemia.Leukemia · 2026Article
- MBNL1 hijacks a structured single-stranded distal DNA element to sustainScience advances · 2026Article
- Deciphering resistance mechanisms to auxin-inducible protein degradation in mammalian cells.The Journal of biological chemistry · 2026Article
- USP52 impedes malignant progression and cell stemness in prostate cancer by deubiquitinating RBM5 to down-regulate NCAPG2.Molecular and cellular biochemistry · 2026Article
- G-patch proteins: important regulators of pre-mRNA splicing and ribosome biogenesis.Frontiers in cell and developmental biology · 2026Review
- RNA-binding motif proteins as context-dependent regulators of tumor-immune crosstalk, genome stability, and therapeutic vulnerabilities in cancer.Frontiers in immunology · 2026Review
- HOXA9 drives lymphatic metastasis by activating the c-MYC-glycolysis-lactate axis in gastric cancer.Journal of translational medicine · 2025Article
- Prospective Analysis of Mesotheliomas in Subjects With BAP1 Cancer Syndrome: Clinical Characteristics and Epigenetic Correlates of Disease.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025Observational
- Deciphering acquired resistance mechanisms to sustained auxin-inducible protein degradation in cells and mice.bioRxiv : the preprint server for biology · 2025Article
- RNA-binding protein RBM5 plays an essential role in acute myeloid leukemia by activating the oncogenic protein HOXA9.Genome biology · 2024Article
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Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe oncogenic protein HOXA9 plays a critical role in leukemia transformation and maintenance, and its aberrant expression is a hallmark of most aggressive acute leukemia. Although inhibiting the upstream regulators of HOXA9 has been proven as a significant therapeutic intervention, the comprehensive regulation network controlling HOXA9 expression in leukemia has not been systematically investigated.
resultsHere, we perform genome-wide CRISPR/Cas9 screening in the HOXA9-driven reporter acute leukemia cells. We identify a poorly characterized RNA-binding protein, RBM5, as the top candidate gene required to maintain leukemia cell fitness. RBM5 is highly overexpressed in acute myeloid leukemia (AML) patients compared to healthy individuals. RBM5 loss triggered by CRISPR knockout and shRNA knockdown significantly impairs leukemia maintenance in vitro and in vivo. Through domain CRISPR screening, we reveal that RBM5 functions through a noncanonical transcriptional regulation circuitry rather than RNA splicing, such an effect depending on DNA-binding domains. By integrative analysis and functional assays, we identify HOXA9 as the downstream target of RBM5. Ectopic expression of HOXA9 rescues impaired leukemia cell proliferation upon RBM5 loss. Importantly, acute protein degradation of RBM5 through auxin-inducible degron system immediately reduces HOXA9 transcription.
conclusionsWe identify RBM5 as a new upstream regulator of HOXA9 and reveal its essential role in controlling the survival of AML. These functional and molecular mechanisms further support RBM5 as a promising therapeutic target for myeloid leukemia treatment.
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