ArticleBlood cancer discovery2023
METTL3-Mediated m6A Modification Controls Splicing Factor Abundance and Contributes to Aggressive CLL.
Article in Blood cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Characterization of METTL3/14-mediated m6A modification in human transcriptome using Nanopore direct RNA sequencing.PLoS genetics · 2026Article
- PLCG2 exon-skipped variants: insights into their potential role in chronic lymphocytic leukemia.Blood advances · 2026Article
- Deacetylation of ACLY Mediates RNA MAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- SF3B1 mutation accelerates the development of CLL via activation of the mTOR pathway.JCI insight · 2025Article
- Advances in lymphoma biomarkers research based on proteomics technology (Review).Oncology reports · 2025Review
- HNRNPC and m6A RNA methylation control oncogenic transcription and metabolism in T-cell leukemia.Blood · 2025Article
- Nanopore direct RNA sequencing of human transcriptomes reveals the complexity of mRNA modifications and crosstalk between regulatory features.Cell genomics · 2025Article
- Aberrant overexpression of m6A writer and reader genes in pediatric B-Cell Acute Lymphoblastic Leukemia (B-ALL).Translational oncology · 2025Article
- CircMVP promotes METTL3 activation mediated CTNNB1 m6A modification in the inhibition of colorectal cancer in B7-H3 dependence antitumor immunity.International journal of biological sciences · 2025Article
- Research progress on m6A and drug resistance in gastrointestinal tumors.Frontiers in pharmacology · 2025Review
- Global transcriptome modulation by xenobiotics: the role of alternative splicing in adaptive responses to chemical exposures.Human genomics · 2024Article
- mEMBO reports · 2024Article
- Engineering Oncogenic Hotspot Mutations on SF3B1 via CRISPR-Directed PRECIS Mutagenesis.Cancer research communications · 2024Article
- Integrative Analysis of Multi-Omics Data to Identify Deregulated Molecular Pathways and Druggable Targets in Chronic Lymphocytic Leukemia.Journal of personalized medicine · 2024Article
- Competition of dualBlood neoplasia · 2024Article
- The role of m6A-associated membraneless organelles in the RNA metabolism processes and human diseases.Theranostics · 2024Review
- Leveraging genomics, transcriptomics and epigenomics to understand chemoimmunotherapy resistance in chronic lymphocytic leukemia.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- SF3B1 mutation and ATM deletion codrive leukemogenesis via centromeric R-loop dysregulation.The Journal of clinical investigation · 2023Article
- Global Shift in Alternative Splicing and Therapeutic Susceptibilities in Leukemia Driven by METTL3 Overexpression.Blood cancer discovery · 2023Article
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21 authors at 4 institutions in 1 country.
Funding
Abstract
RNA splicing dysregulation underlies the onset and progression of cancers. In chronic lymphocytic leukemia (CLL), spliceosome mutations leading to aberrant splicing occur in ∼20% of patients. However, the mechanism for splicing defects in spliceosome-unmutated CLL cases remains elusive. Through an integrative transcriptomic and proteomic analysis, we discover that proteins involved in RNA splicing are posttranscriptionally upregulated in CLL cells, resulting in splicing dysregulation. The abundance of splicing complexes is an independent risk factor for poor prognosis. Moreover, increased splicing factor expression is highly correlated with the abundance of METTL3, an RNA methyltransferase that deposits N6-methyladenosine (m6A) on mRNA. METTL3 is essential for cell growth in vitro and in vivo and controls splicing factor protein expression in a methyltransferase-dependent manner through m6A modification-mediated ribosome recycling and decoding. Our results uncover METTL3-mediated m6A modification as a novel regulatory axis in driving splicing dysregulation and contributing to aggressive CLL. SIGNIFICANCE: METTL3 controls widespread splicing factor abundance via translational control of m6A-modified mRNA, contributes to RNA splicing dysregulation and disease progression in CLL, and serves as a potential therapeutic target in aggressive CLL. See related commentary by Janin and Esteller, p. 176. This article is highlighted in the In This Issue feature, p. 171.
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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.