Efficient use of a translation start codon in BDNF exon I
Efficient use of a translation start codon in BDNF exon I
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DOI:
10.1111/jnc.13124
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发表时间:
2015-09-01
影响因子:
4.7
通讯作者:
Timmusk, Tonis
中科院分区:
文献类型:
--
作者:
Koppel, Indrek;Tuvikene, Juergen;Timmusk, Tonis
The brain-derived neurotrophic factor (BDNF) gene contains a number of 50 exons alternatively spliced with a common 30 exon. BDNF protein is synthesized from alternative transcripts as a prepro-precursor encoded by the common 30 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 50 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.