ArticleGene2011
An SRp75/hnRNPG complex interacting with hnRNPE2 regulates the 5' splice site of tau exon 10, whose misregulation causes frontotemporal dementia.
Article in Gene, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
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- Mechanistic insights into the basis of widespread RNA localization.Nature cell biology · 2024Review
- The Landscape of m6A Regulators in Multiple Brain Regions of Alzheimer's Disease.Molecular neurobiology · 2023Article
- Towards understandings of serine/arginine-rich splicing factors.Acta pharmaceutica Sinica. B · 2023Review
- Genetic Mapping of Behavioral Traits Using the Collaborative Cross Resource.International journal of molecular sciences · 2022Article
- Tau interactome and RNA binding proteins in neurodegenerative diseases.Molecular neurodegeneration · 2022Review
- Functional analysis of the stable phosphoproteome reveals cancer vulnerabilities.Bioinformatics (Oxford, England) · 2022Article
- Genes for RNA-binding proteins involved in neural-specific functions and diseases are downregulated in Rubinstein-Taybi iNeurons.Neural regeneration research · 2022Article
- The SRSF4-GAS5-Glucocorticoid Receptor Axis Regulates Ventricular Hypertrophy.Circulation research · 2021Article
- The role of hnRNPs in frontotemporal dementia and amyotrophic lateral sclerosis.Acta neuropathologica · 2020Review
- Hyperconserved Elements in Human 5'UTRs Shape Essential Post-transcriptional Regulatory Networks.Frontiers in molecular biosciences · 2020Article
- Physiological and Pathological Function of Serine/Arginine-Rich Splicing Factor 4 and Related Diseases.BioMed research international · 2018Review
- RNA localization is a key determinant of neurite-enriched proteome.Nature communications · 2017Article
- N6-methyladenosine alters RNA structure to regulate binding of a low-complexity protein.Nucleic acids research · 2017Article
- Single neuron transcriptomics identify SRSF/SR protein B52 as a regulator of axon growth and Choline acetyltransferase splicing.Scientific reports · 2016Article
- The hnRNP family: insights into their role in health and disease.Human genetics · 2016Review
- RNA Binding Proteins RZ-1B and RZ-1C Play Critical Roles in Regulating Pre-mRNA Splicing and Gene Expression during Development in Arabidopsis.The Plant cell · 2016Article
- Functional Analysis of Mutations in Exon 9 of NF1 Reveals the Presence of Several Elements Regulating Splicing.PloS one · 2015Article
- Article
- The adipogenic transcriptional cofactor ZNF638 interacts with splicing regulators and influences alternative splicing.Journal of lipid research · 2014Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
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Abstract
Tau is a neuronal-specific microtubule-associated protein that plays an important role in establishing neuronal polarity and maintaining the axonal cytoskeleton. Aggregated tau is the major component of neurofibrillary tangles (NFTs), structures present in the brains of people affected by neurodegenerative diseases called tauopathies. Tauopathies include Alzheimer's disease (AD), frontotemporal dementia with Parkinsonism (FTDP-17), the early onset dementia observed in Down syndrome (DS; trisomy 21) and the dementia component of myotonic dystrophy type 1 (DM1). Splicing misregulation of adult-specific exon 10, which codes for a microtubule binding domain, results in expression of abnormal ratios of tau isoforms, leading to FTDP-17. Positions 3 to 19 of the intron downstream of exon 10 define a hotspot of splicing regulation: the region diverges between humans and rodents, and point mutations within it result in tauopathies. In this study, we investigated three regulators of exon 10 splicing: serine/arginine-rich protein SRp75 and heterogeneous nuclear ribonucleoproteins hnRNPG and hnRNPE2. SRp75 and hnRNPG inhibit splicing of exon 10 whereas hnRNPE2 activates it. Using co-transfections, co-immunoprecipitations and RNAi we discovered that SRp75 binds to the proximal downstream intron of tau exon 10 at the FTDP-17 hotspot region; and that hnRNPG and hnRNPE2 interact with SRp75. Thus, increased exon 10 inclusion in FTDP mutants may arise from weakened SRp75 binding. This work provides insights into the splicing regulation of the tau gene and into possible strategies for correcting the imbalance in tauopathies caused by changes in the ratio of exon 10.
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