ANALYSIS OF THE NEURONAL PROMOTER OF THE RAT AROMATIC L-AMINO-ACID DECARBOXYLASE GENE

The rat aromatic L-amino acid decarboxylase (AADC) gene contains alter native promoters directing expression of neuronal and nonneuronal mRNA s that differ only in their 5' untranslated regions (UTRs). We have an alyzed the expression of the neuronal promoter of the AADC gene in cel ls synthesizing catecholamines and serotonin, as well as in non-AADC-e xpressing cells. We demonstrate the use of the neuronal-specific UTR i n individual dopamine-, norepinephrine-, and serotonin-containing neur ons. Transfection analyses show that the rat AADC neuronal promoter, c ontaining 2,400 bp upstream of the transcription start site and includ ing the 68-bp untranslated exon 2, can activate transcription from a r eporter gene in both catecholaminergic and serotonergic cell lines. Th ese analyses identified several positive and negative cis-active eleme nts within this region. Unexpectedly, we observed that this promoter, when removed from its native context within the AADC gene, can also di rect expression of a reporter gene in cells that do not normally expre ss AADC mRNA. These results suggest that tissue-specific expression of the neuronal promoter may not be controlled by cis-active elements wi thin the first 2,400 bp of the promoter. Additional information may be required to restrict neuronal promoter expression to appropriate cell types. This regulatory information could reside elsewhere within the promoter, within introns, or may be provided by interactions between t he two AADC promoters.