Dissecting the human BDNF locus: bidirectional transcription, complex splicing, and multiple promoters.
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.
Pruunsild
Priit
P
Department of Gene Technology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 19086, Estonia.
Kazantseva
Anna
A
Aid
Tamara
T
Palm
Kaia
K
Timmusk
Tõnis
T
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001921:Brain / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000502:physiology*; D003001:Cloning, Molecular; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D014018:Tissue Distribution
D019208:Brain-Derived Neurotrophic Factor; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger