Pruunsild Priit, Kazantseva Anna, Aid Tamara, Palm Kaia, Timmusk Tõnis
Department of Gene Technology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 19086, Estonia.
Genomics. 2007 Sep;90(3):397-406. doi: 10.1016/j.ygeno.2007.05.004. Epub 2007 Jul 12.
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.
脑源性神经营养因子（BDNF）是神经营养因子家族神经生长因子的成员之一，在神经系统的发育、生理和病理过程中发挥着核心作用。我们已经阐明了人类BDNF基因的结构，鉴定了可变转录本，并研究了它们在成人组织和脑区中的表达。此外，确定了人类BDNF转录本的转录起始位点，并在瞬时过表达实验中分析了BDNF启动子的活性。我们的结果表明，人类BDNF基因有11个外显子和9个功能性启动子，这些启动子在组织和脑区中具有特异性使用。此外，从抗BDNF基因（批准的基因符号BDNFOS）在BDNF基因座中转录出显示复杂剪接和表达模式的非编码天然反义RNA。我们表明，BDNF和抗BDNF转录本在体内大脑中形成双链RNA双链体，这表明抗BDNF在调节人类BDNF表达中具有重要作用。
