Dissecting the human BDNF locus: Bidirectional transcription, complex splicing, and multiple promoters

By P. Pruunsild, Anna Kazantseva1, Tamara Aid, Kaia Palm, T. Timmusk. Genomics, 2007

718 citations recorded by the source corpus.

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.

Subfields: Biomaterials, Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d0a2b1fedd5909076940f7c1f409ada3fdc75cbb

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Citations in the corpus

BDNF — a key transducer of antidepressant effects (2015, background): “The BDNF gene has nine promoters that drive expression of distinct Bdnf transcripts that each encode the same BDNF protein (Aid et al., 2007; Pruunsild et al., 2007).”
BDNF: A Key Factor with Multipotent Impact on Brain Signaling and Synaptic Plasticity (2017, background): “The human BDNF gene consists of 11 exons, and its different splicing enables formation of transcripts specific to various tissues and responsive to different stimuli (Pruunsild et al. 2007).”
Molecular mechanisms and potential therapeutical targets in Huntington's disease. (2010, background): “The different promoter-like sequences upstream of exons I-IX act independently and modulate the transcription of mRNA I-IX in a stimulus- and developmental-specific manner (2, 453, 580, 581).”
Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer (2020, background): “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].”
Post-synaptic BDNF-TrkB Signaling in Synapse Maturation, Plasticity and Disease (2010, neutral): “For example see (Pruunsild et al., 2007; Tian et al., 2009).”
GDNF, NGF and BDNF as therapeutic options for neurodegeneration. (2013, background): “The BDNF gene is one of the most tightly regulated genes, with 11 exons and 9 functional promoters (Pruunsild et al, 2007) and gives rise to approximately 34 transcripts (Gabriele & Tongiorgi, 2009) in response to various stimuli.”
Brain-derived neurotrophic factor and its clinical implications (2015, background): “The BDNF expression levels are low during fetal development, markedly increase after birth, and then decrease in adults [17–19].”