ArticleThe Journal of biological chemistry2015
HIV-1-Tat Protein Inhibits SC35-mediated Tau Exon 10 Inclusion through Up-regulation of DYRK1A Kinase.
Article in The Journal of biological chemistry, 2015. 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, 25 citations in OpenAlex.
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Convergence of neuroinflammation across major neurotropic viral exposomes in AD and ADRD.Journal of neuroinflammation · 2026Review
- Implications of virus-induced stress granules in tauopathies.Translational neurodegeneration · 2026Review
- Enhanced packaging of U6 small nuclear RNA and splicing-related proteins into extracellular vesicles during HIV infection.Science advances · 2025Article
- Towards understandings of serine/arginine-rich splicing factors.Acta pharmaceutica Sinica. B · 2023Review
- Progressive Degeneration and Adaptive Excitability in Dopamine D1 and D2 Receptor-Expressing Striatal Neurons Exposed to HIV-1 Tat and Morphine.Cellular and molecular neurobiology · 2023Article
- Phosphorylation regulates arginine-rich RNA-binding protein solubility and oligomerization.The Journal of biological chemistry · 2021Article
- HIV-1 and drug abuse comorbidity: Lessons learned from the animal models of NeuroHIV.Neuroscience letters · 2021Review
- Morphine and HIV-1 Tat interact to cause region-specific hyperphosphorylation of tau in transgenic mice.Neuroscience letters · 2021Article
- Interplay Between CMGC Kinases Targeting SR Proteins and Viral Replication: Splicing and Beyond.Frontiers in microbiology · 2021Review
- Splicing factor SRSF2-centric gene regulation.International journal of biological sciences · 2021Review
- Skipped Over: Tuning Natural Killer Cells Toward HIV Through Alternative Splicing.AIDS research and human retroviruses · 2020Article
- Article
- HIV and Alzheimer's disease: complex interactions of HIV-Tat with amyloid β peptide and Tau protein.Journal of neurovirology · 2019Review
- Viral modulation of cellular RNA alternative splicing: A new key player in virus-host interactions?Wiley interdisciplinary reviews. RNA · 2019Review
- RNA Splicing: A New Paradigm in Host-Pathogen Interactions.Journal of molecular biology · 2019Review
- Glia-to-neuron transfer of miRNAs via extracellular vesicles: a new mechanism underlying inflammation-induced synaptic alterations.Acta neuropathologica · 2018Article
- Doxycycline-inducible and astrocyte-specific HIV-1 Tat transgenic mice (iTat) as an HIV/neuroAIDS model.Journal of neurovirology · 2018Review
- Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The HIV-1 transactivator protein Tat is implicated in the neuronal damage that contributes to neurocognitive impairment affecting people living with HIV/AIDS. Aberrant splicing of TAU exon 10 results in tauopathies characterized by alterations in the proportion of TAU isoforms containing three (3R) or four (4R) microtubule-binding repeats. The splicing factor SC35/SRSF2 binds to nuclear RNA and facilitates the incorporation of exon 10 in the TAU molecule. Here, we utilized clinical samples, an animal model, and neuronal cell cultures and found that Tat promotes TAU 3R up-regulation through increased levels of phosphorylated SC35, which is retained in nuclear speckles. This mechanism involved Tat-mediated increased expression of DYRK1A and was prevented by DYRK1A silencing. In addition, we found that Tat associates with TAU RNA, further demonstrating that Tat interferes with host RNA metabolism in the absence of viral infection. Altogether, our data unravel a novel mechanism of Tat-mediated neuronal toxicity through dysregulation of the SC35-dependent alternative splicing of TAU exon 10. Furthermore, the increased immunostaining of DYRK1A in HIV+ brains without pathology points at dysregulation of DYRK1A as an early event in the neuronal complications of HIV infection.
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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.