PMID- 25868795
OWN - NLM
STAT- MEDLINE
DCOM- 20151214
LR  - 20220309
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Linking)
VI  - 134
IP  - 6
DP  - 2015 Sep
TI  - Efficient use of a translation start codon in BDNF exon I.
PG  - 1015-25
LID - 10.1111/jnc.13124 [doi]
AB  - 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.
CI  - (c) 2015 International Society for Neurochemistry.
FAU - Koppel, Indrek
AU  - Koppel I
AD  - Department of Gene Technology, Tallinn University of Technology, Tallinn, 
      Estonia.
FAU - Tuvikene, Jurgen
AU  - Tuvikene J
AD  - Department of Gene Technology, Tallinn University of Technology, Tallinn, 
      Estonia.
FAU - Lekk, Ingrid
AU  - Lekk I
AD  - Department of Gene Technology, Tallinn University of Technology, Tallinn, 
      Estonia.
FAU - Timmusk, Tonis
AU  - Timmusk T
AD  - Department of Gene Technology, Tallinn University of Technology, Tallinn, 
      Estonia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150427
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Codon, Initiator)
RN  - 0 (Protein Isoforms)
SB  - IM
MH  - Alternative Splicing
MH  - Animals
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis/*genetics
MH  - Codon, Initiator/*genetics
MH  - Exons/*genetics
MH  - Protein Biosynthesis/*genetics
MH  - Protein Isoforms/biosynthesis/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transfection
OTO - NOTNLM
OT  - BDNF
OT  - secretion
OT  - signal peptide
OT  - translation
EDAT- 2015/04/15 06:00
MHDA- 2015/12/15 06:00
CRDT- 2015/04/15 06:00
PHST- 2015/01/29 00:00 [received]
PHST- 2015/04/01 00:00 [revised]
PHST- 2015/04/02 00:00 [accepted]
PHST- 2015/04/15 06:00 [entrez]
PHST- 2015/04/15 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - 10.1111/jnc.13124 [doi]
PST - ppublish
SO  - J Neurochem. 2015 Sep;134(6):1015-25. doi: 10.1111/jnc.13124. Epub 2015 Apr 27.