ArticleThe Journal of biological chemistry2009
Functional role of transcriptional factor TBX5 in pre-mRNA splicing and Holt-Oram syndrome via association with SC35.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- Context-dependent T-BOX transcription factor family: from biology to targeted therapy.Cell communication and signaling : CCS · 2024Review
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- Lateral thinking in syndromic congenital cardiovascular disease.Disease models & mechanisms · 2023Article
- Cohesin regulates alternative splicing.Science advances · 2023Article
- Post-Transcriptional Modification by Alternative Splicing and Pathogenic Splicing Variants in Cardiovascular Development and Congenital Heart Defects.International journal of molecular sciences · 2023Review
- Receptor and Molecular Mechanism of AGGF1 Signaling in Endothelial Cell Functions and Angiogenesis.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Angiogenic factor AGGF1 acts as a tumor suppressor by modulating p53 post-transcriptional modifications and stability via MDM2.Cancer letters · 2021Article
- QKI is a critical pre-mRNA alternative splicing regulator of cardiac myofibrillogenesis and contractile function.Nature communications · 2021Article
- mRNA Metabolism in Cardiac Development and Disease: Life After Transcription.Physiological reviews · 2020Review
- Long noncoding RNAThe Journal of biological chemistry · 2019Article
- SRSF6 is upregulated in asthmatic horses and involved in the MYH11 SMB expression.Physiological reports · 2018Article
- Gene Regulatory Network Perturbation by Genetic and Epigenetic Variation.Trends in biochemical sciences · 2018Review
- NUP155 insufficiency recalibrates a pluripotent transcriptome with network remodeling of a cardiogenic signaling module.BMC systems biology · 2018Article
- Beyond Transcription: Roles of Transcription Factors in Pre-mRNA Splicing.Chemical reviews · 2018Review
- Targeting AGGF1 (angiogenic factor with G patch and FHA domains 1) for Blocking Neointimal Formation After Vascular Injury.Journal of the American Heart Association · 2017Article
- Haploinsufficiency of Klippel-Trenaunay syndrome gene Aggf1 inhibits developmental and pathological angiogenesis by inactivating PI3K and AKT and disrupts vascular integrity by activating VE-cadherin.Human molecular genetics · 2016Article
- Coronary artery disease susceptibility gene ADTRP regulates cell cycle progression, proliferation, and apoptosis by global gene expression regulation.Physiological genomics · 2016Article
- αB-Crystallin Interacts with Nav1.5 and Regulates Ubiquitination and Internalization of Cell Surface Nav1.5.The Journal of biological chemistry · 2016Article
- Putative Breast Cancer Driver Mutations in TBX3 Cause Impaired Transcriptional Repression.Frontiers in oncology · 2015Article
- Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TBX5 is a T-box transcriptional factor required for cardiogenesis and limb development. TBX5 mutations cause Holt-Oram syndrome characterized by congenital heart defects and upper limb deformations. Here we establish a novel function for TBX5 in pre-mRNA splicing, and we show that this function is relevant to the pathogenesis of Holt-Oram syndrome, providing a novel pathogenic mechanism for the disease. Proteomics in combination with affinity purification identifies splicing factor SC35 as a candidate TBX5-associating protein. Co-immunoprecipitation and glutathione S-transferase pulldown assays confirm the complex formation between TBX5 and SC35. TBX5 can bind to RNA homopolymers (polyribonucleotides) and to the 5'-splice site, which overrides the binding of SC35 to the same RNA. Overexpression of TBX5 increases the efficiency of pre-mRNA splicing and regulates alternative splice site selection. However, co-expression of TBX5 and SC35 antagonizes each other's positive effect on splicing. The most severe TBX5 mutation, G80R, with complete penetrance of the cardiac phenotype, strongly affects pre-mRNA splicing, whereas other mutations with incomplete penetrance of the cardiac phenotype, including R237Q, do not alter the splicing activity of TBX5. This study establishes TBX5 as the first cardiac gene and the first human disease gene with dual roles in both transcriptional activation and pre-mRNA splicing.
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