title: Efficient use of a translation start codon in BDNF exon I.
abstract: The brain-derived neurotrophic factor (BDNF) gene contains a number of 5' exons alternatively spliced with a common 3' exon. BDNF protein is synthesized from alternative transcripts as a prepro-precursor encoded by the common 3' exon IX, which has a translation start site 21 bp downstream of the splicing site. BDNF mRNAs containing exon I are an exception to this arrangement as the last three nucleotides of this exon constitute an in-frame AUG. Here, we show that this AUG is efficiently used for translation initiation in PC12 cells and cultured cortical neurons. Use of exon I-specific AUG produces higher levels of BDNF protein than use of the common translation start site, resulting from a higher translation rate. No differences in protein degradation, constitutive or regulated secretion were detected between BDNF isoforms with alternative 5' termini. As the BDNF promoter preceding exon I is known to be highly regulated by neuronal activity, our results suggest that the function of this translation start site may be efficient stimulus-dependent synthesis of BDNF protein. The brain-derived neurotrophic factor (BDNF) gene contains multiple untranslated 5' exons alternatively spliced to one common protein-coding 3' exon. However, exon I contains an in-frame ATG in a favorable translation context. Here, we show that use of this ATG is associated with more efficient protein synthesis than the commonly used ATG in exon IX.
authors: Department of Gene Technology, Tallinn University of Technology, Tallinn, Estonia.
authors: Indrek
authors: I
authors: Koppel
authors: Department of Gene Technology, Tallinn University of Technology, Tallinn, Estonia.
authors: Jürgen
authors: J
authors: Tuvikene
authors: Department of Gene Technology, Tallinn University of Technology, Tallinn, Estonia.
authors: Ingrid
authors: I
authors: Lekk
authors: Department of Gene Technology, Tallinn University of Technology, Tallinn, Estonia.
authors: Tõnis
authors: T
authors: Timmusk
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics*; D018387:Codon, Initiator / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D014176:Protein Biosynthesis / Q000235:genetics*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018387:Codon, Initiator; D020033:Protein Isoforms
keywords: BDNF; secretion; signal peptide; translation