TISSUE-SPECIFIC EXPRESSION AND ALTERNATIVE MESSENGER-RNA PROCESSING OF THE MAMMALIAN ACETYLCHOLINESTERASE GENE

This study examines the tissue specificity and the gene products arising from alternative mRNA processing of the mammalian acetylcholinesterase gene. By splicing either alternative exons 5 or 6 in the mouse and human genes directly to the invariant exons (exons 2, 3, and 4), we show that the acetylcholinesterase species expressed by transfected recombinant DNA have the properties expected for the respective enzyme forms found in tissue. Antisense mRNA derived from these cDNAs has been employed to examine differential splicing in various tissues. In most cells, the hydrophilic form of AChE encoded by the exon 4 to exon 6 splice to form the mRNA is the predominant species. However, splicing of exon 4 to exon 5, yielding a mRNA encoding the glycophospholipid-linked form of acetylcholinesterase, is seen primarily in erythroid and to a lesser extent in AtT-20 cells. Only small amounts of this mRNA species appear in some other cells in culture. A novel third mRNA species, which arises from an extension of exon 4 without splicing to a downstream exon, is seen in mouse erythroid but not in human erythroid cells. A cDNA encoding this species when expressed in COS cells gives rise to a unique hydrophilic, secreted form of acetylcholinesterase. Transfection of a human genomic clone into mouse erythroleukemia cells does not result in the appearance of a mRNA species with an extension of exon 4 as seen with the endogenous mouse gene. Hence, differential splicing between the mouse and human genes appears intrinsic to the coding sequence and is not dependent solely on specific factors in the mouse erythroleukemia cell.