Dissecting the human BDNF locus: Bidirectional transcription, complex splicing, and multiple promoters
Open accessAbstract
Brain-derived neurotrophic factor (BDNF), a member of the nerve growth factor family of neurotrophins, has central roles in the development, physiology, and pathology of the nervous system. We have elucidated the structure of the human BDNF gene, identified alternative transcripts, and studied their expression in adult human tissues and brain regions. In addition, the transcription initiation sites for human BDNF transcripts were determined and the activities of BDNF promoters were analyzed in transient overexpression assays. Our results show that the human BDNF gene has 11 exons and nine functional promoters that are used tissue and brain-region specifically. Furthermore, noncoding natural antisense RNAs that display complex splicing and expression patterns are transcribed in the BDNF gene locus from the antiBDNF gene (approved gene symbol BDNFOS). We show that BDNF and antiBDNF transcripts form dsRNA duplexes in the brain in vivo, suggesting an important role for antiBDNF in regulating BDNF expression in human.
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BDNF has a complex gene structure with 11 different exons in humans, nine different exons in rodents, and nine alternative promoters for both groups.
“Further studies, published in 2007, clarified that BDNF has a complex gene structure with 11 different exons in humans, nine different exons in rodents, and nine alternative promoters for both groups [32,33].”
From Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer (2020) · cites this paper as [33]
The Discussion states that human BDNF has 11 exons and nine functional promoters, and that it has two more exons than rodent BDNF. The Abstract describes eight rodent 5′ exons with separate promoters and one coding exon, supporting nine rodent exons but not nine rodent promoters. The claim's promoter count for rodents is therefore unsupported by this paper. (LLM, conf=0.88)
Experimental — accuracy not yet measuredHuman heart tissue expresses high levels of BDNF isoforms containing exon IV and exon IX.
“Human heart tissue, instead, expresses high levels of BDNF isoforms containing exon IV and exon IX [33].”
From Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer (2020) · cites this paper as [33]
The Results section on adult human tissues reports high expression in the heart of BDNF transcripts containing exon IXabcd, supporting the exon IX part of the claim. It identifies exon VI—not exon IV—as the other highly expressed heart transcript, and the Discussion describes exon IV transcripts as mostly brain-specific. Page numbers are not available in the supplied passages. (LLM, conf=0.90)
Experimental — accuracy not yet measuredIn human brain tissues, all BDNF exons are expressed, but to different degrees and in different brain structures.
“For instance, in human brain tissues, all exons are expressed, but to different degrees and in different brain structures [33].”
From Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer (2020) · cites this paper as [33]
Exon IX is present in all BDNF mRNA isoforms.
“Exon IX is present in all BDNF mRNA isoforms.”
From Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer (2020) · cites this paper as [33]
The coding sequence of BDNF is located in exon IX in both human and rodents.
“Despite this complexity, the coding sequence is located in exon IX in both human and rodents.”
From Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer (2020) · cites this paper as [33]
Exon IX includes the common sequence that encodes for the proBDNF protein.
“The latter includes the common sequence that encodes for the proBDNF protein.”
From Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer (2020) · cites this paper as [33]
The human BDNF gene has nine promoters that are used in specific tissues and brain regions.
“For example, the human brain-derived neurotrophic factor (BDNF) gene has nine promoters that are used in specific tissues and brain-regions (Pruunsild et al., 2007).”
From Genetic Changes Shaping the Human Brain (2015) · cites this paper as Pruunsild et al., 2007
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- Authors
- Pruunsild, P., Kazantseva, A., Aid, T., Palm, K., & Timmusk, T.
- Affiliations
- Tallinn University of Technology (EE)
- Corresponding author
- Timmusk, Tõnis
- Venue
- Genomics
- Publisher
- Elsevier BV
- Published
- 2007-09
- Volume
- 90
- Issue
- 3
- Pages
- 397-406
- ISSN
- 0888-7543 (ISSN-L)
- PMC
- PMC2568880
- OpenAlex
- W1982889157
- Cited by
- 699
- References
- 39
- Citations by year
- 2026: 17 · 2025: 14 · 2024: 31 · 2023: 43 · 2022: 50 · 2021: 39 · 2020: 36 · 2019: 44 · 2018: 40 · 2017: 38 · 2016: 55 · 2015: 48 · 2014: 48 · 2013: 45 · 2012: 37
- FWCI
- 10.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Genomics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Haridus- ja Teadusministeerium (0222602)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- brain-derived neurotrophic factor, bidirectional transcription, alternative splicing, multiple promoters, transcription start sites, double-stranded RNA, gene structure, tissue-specific gene expression, brain region-specific expression, neurotrophins
- MeSH terms
- Amino Acid Sequence, Brain, Cloning, Molecular, Exons, Gene Expression Regulation, Humans, Models, Genetic, Molecular Sequence Data, Plasmids, Promoter Regions, Genetic, RNA, Messenger, Tissue Distribution, Oligonucleotides, Antisense, Alternative Splicing, Brain-Derived Neurotrophic Factor
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