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Multiple promoters direct tissue-specific expression of the rat BDNF gene

Identifieur interne : 001014 ( Main/Exploration ); précédent : 001013; suivant : 001015

Multiple promoters direct tissue-specific expression of the rat BDNF gene

Auteurs : T Nis Timmusk ; Kaia Palm ; Madis Metsis ; T Nu Reintam ; Viiu Paalme ; Mart Saarma ; H Kan Persson

Source :

RBID : ISTEX:38474E75C82DBB1E9D4CB7FF73F1903AB4B3BBB6

Abstract

Brain-derived neurotrophic factor (BDNF) supports the survival of a specific set of neurons in the vertebrate nervous system. Here we show that the rat BDNF gene consists of four short 5′ exons and one 3′ exon encoding the mature BDNF protein. Eight different BDNF mRNAs with four different 5′ ends and two alternative polyadenylation sites are transcribed from this gene. BDNF mRNAs containing exons I, II, and III are expressed predominantly in the brain, whereas exon IV transcripts predominate in the lung and heart. mRNAs containing exons I, II, and III increase markedly in the brain after kainic acid-induced seizures, whereas exon IV mRNA increases only slightly. Several transcription initiation sites were mapped upstream of the four 5′ exons, and transfection of promoter-reporter gene constructs confirmed that these sequences act as promoters. Combined, the data demonstrate that alternative usage of four promoters within the BDNF gene and differential splicing control tissue-specific and seizure-induced expression of BDNF mRNA.


Url:
DOI: 10.1016/0896-6273(93)90335-O


Affiliations:


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<div type="abstract" xml:lang="en">Brain-derived neurotrophic factor (BDNF) supports the survival of a specific set of neurons in the vertebrate nervous system. Here we show that the rat BDNF gene consists of four short 5′ exons and one 3′ exon encoding the mature BDNF protein. Eight different BDNF mRNAs with four different 5′ ends and two alternative polyadenylation sites are transcribed from this gene. BDNF mRNAs containing exons I, II, and III are expressed predominantly in the brain, whereas exon IV transcripts predominate in the lung and heart. mRNAs containing exons I, II, and III increase markedly in the brain after kainic acid-induced seizures, whereas exon IV mRNA increases only slightly. Several transcription initiation sites were mapped upstream of the four 5′ exons, and transfection of promoter-reporter gene constructs confirmed that these sequences act as promoters. Combined, the data demonstrate that alternative usage of four promoters within the BDNF gene and differential splicing control tissue-specific and seizure-induced expression of BDNF mRNA.</div>
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