ArticlePloS one2010
Alternative splicing and extensive RNA editing of human TPH2 transcripts.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 78 citations in OpenAlex.
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- Identification of blood transcriptome modules associated with suicidal ideation in patients with major depressive disorder.Scientific reports · 2025Article
- Viral N protein hijacks deaminase-containing RNA granules to enhance SARS-CoV-2 mutagenesis.The EMBO journal · 2024Article
- No association between peripheral serotonin-gene-related DNA methylation and brain serotonin neurotransmission in the healthy and depressed state.Clinical epigenetics · 2024Article
- Association of Functional Polymorphism inGenes · 2023Article
- Vaccinia-related kinase 2 variants differentially affect breast cancer growth by regulating kinase activity.Oncology research · 2023Article
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- Serotonin system in the human placenta - the knowns and unknowns.Frontiers in endocrinology · 2022Review
- A mark of disease: how mRNA modifications shape genetic and acquired pathologies.RNA (New York, N.Y.) · 2021Review
- Serotonin deficiency induced after brain maturation rescues consequences of early life adversity.Scientific reports · 2021Article
- Transcriptome-Wide Identification of G-to-A RNA Editing in Chronic Social Defeat Stress Mouse Models.Frontiers in genetics · 2021Article
- Small RNAs, Big Diseases.International journal of molecular sciences · 2020Review
- WidespreadRNA (New York, N.Y.) · 2019Article
- Brain region-specific alterations of RNA editing in PDE8A mRNA in suicide decedents.Translational psychiatry · 2019Article
- Review
- A Novel Alternative Splicing Mechanism That Enhances Human 5-HT1A Receptor RNA Stability Is Altered in Major Depression.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Effect of childhood general traumas on suicide attempt depends on TPH2 and ADARB1 variants in psychiatric patients.Journal of neural transmission (Vienna, Austria : 1996) · 2017Article
- Article
- Sex differences modulating serotonergic polymorphisms implicated in the mechanistic pathways of risk for depression and related disorders.Journal of neuroscience research · 2017Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain serotonin (5-HT) neurotransmission plays a key role in the regulation of mood and has been implicated in a variety of neuropsychiatric conditions. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of 5-HT. Recently, we discovered a second TPH isoform (TPH2) in vertebrates, including man, which is predominantly expressed in brain, while the previously known TPH isoform (TPH1) is primarly a non-neuronal enzyme. Overwhelming evidence now points to TPH2 as a candidate gene for 5-HT-related psychiatric disorders. To assess the role of TPH2 gene variability in the etiology of psychiatric diseases we performed cDNA sequence analysis of TPH2 transcripts from human post mortem amygdala samples obtained from individuals with psychiatric disorders (drug abuse, schizophrenia, suicide) and controls. Here we show that TPH2 exists in two alternatively spliced variants in the coding region, denoted TPH2a and TPH2b. Moreover, we found evidence that the pre-mRNAs of both splice variants are dynamically RNA-edited in a mutually exclusive manner. Kinetic studies with cell lines expressing recombinant TPH2 variants revealed a higher activity of the novel TPH2B protein compared with the previously known TPH2A, whereas RNA editing was shown to inhibit the enzymatic activity of both TPH2 splice variants. Therefore, our results strongly suggest a complex fine-tuning of central nervous system 5-HT biosynthesis by TPH2 alternative splicing and RNA editing. Finally, we present molecular and large-scale linkage data evidencing that deregulated alternative splicing and RNA editing is involved in the etiology of psychiatric diseases, such as suicidal behaviour.
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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.