A UNIQUE GENE ORGANIZATION FOR 2 CHOLINERGIC MARKERS, CHOLINE-ACETYLTRANSFERASE AND A PUTATIVE VESICULAR TRANSPORTER OF ACETYLCHOLINE

Choline acetyltransferase (ChAT) is the biosynthetic enzyme of acetylc holine. In mammalian tissues, it is encoded by multiple mRNAs with dif ferent 5'-ends. This diversity results from the alternative usage of t hree promoters and from differential splicing events. Here, we show th at the first intron of the rat ChAT gene contains an open reading fram e that encodes a potential vesicular acetylcholine transporter based o n the following criteria. (i) The encoded protein is structurally simi lar to transporter proteins, the highest identity being found with the vesicular acetylcholine transporters from Torpedo and Caenorhabditis elegans (77 and 56%, respectively, in 352 amino acids). (ii) The corre sponding mRNAs exhibit a cholinergic expression profile. Amplification experiments with spinal cord cDNA revealed that at least three mRNAs encode this transporter. Two contain the same 5' non-coding region as two ChAT mRNAs and, therefore, are derived from the ChAT transcription unit by alternative splicing. The third mRNA may be transcribed from an additional internal promoter.