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.