Efficient use of a translation start codon in BDNF exon I

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 mRNA s 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 PC 12 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.