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

Dissecting the human BDNF locus: bidirectional transcription, complex splicing, and multiple promoters.
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DOI:
10.1016/j.ygeno.2007.05.004
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发表时间:
2007-09
期刊:
影响因子:
4.4
通讯作者:
Timmusk, Tonis
Timmusk, Tonis
中科院分区:
生物学3区
文献类型:
--
作者:
Pruunsild, Priit;Kazantseva, Anna;Aid, Tamara;Palm, Kaia;Timmusk, Tonis

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脑源性神经营养因子 (BDNF) 是神经营养因子神经生长因子家族的成员,在神经系统的发育、生理和病理中发挥着核心作用。我们阐明了人类 BDNF 基因的结构,鉴定了替代转录物,并研究了它们在成人组织和大脑区域中的表达。此外,还确定了人 BDNF 转录物的转录起始位点,并在瞬时过表达测定中分析了 BDNF 启动子的活性。我们的结果表明,人类 BDNF 基因具有 11 个外显子和 9 个专门用于组织和大脑区域的功能启动子。此外,显示复杂剪接和表达模式的非编码天然反义RNA在来自抗BDNF基因(批准的基因符号BDNFOS)的BDNF基因座中转录。我们发现 BDNF 和 antiBDNF 转录物在体内大脑中形成 dsRNA 双链体,这表明 antiBDNF 在调节人类 BDNF 表达中发挥着重要作用。
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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