TISSUE-SPECIFIC ALTERNATIVE SPLICING OF SHAKER POTASSIUM CHANNEL TRANSCRIPTS RESULTS FROM DISTINCT MODES OF REGULATING 3'-SPLICE CHOICE

Alternative splicing of precursor RNA enables a single gene to encode multiple protein isoforms with different functional characteristics an d tissue distributions. Differential splicing of Drosophila Shaker (Sh ) gene transcripts regulates the tissue-specific expression of kinetic ally distinct potassium ion channels throughout development. Regulatio n of Sh alternative splicing is being examined in germline transforman ts using lacZ as a reporter gene. P-element constructs were generated in which one or both of the two mutually exclusive Sh 3' acceptor site s were positioned in the same translational reading frame as the lacZ coding sequences. The constructs were introduced into the germline and the transgenic animals examined for tissue-specific beta-galactosidas e expression patterns. Some tissues exhibit ''promiscuous'' splicing; these tissues are competent to splice to either 3' acceptor even when both are present on the same pre-mRNA. In other tissues splice choice results from competition between the two 3' sites; these tissues can s plice to either site when it is the only available 3' acceptor, but wh en given a choice will splice to only one of the two 3' accepters. In some tissues, splicing occurs exclusively at only one of the 3' accept or sites; these tissues are not competent to splice to one of the site s even if it is the only 3' acceptor present on the pre-mRNA. These re sults suggests that multiple, distinct regulatory modes are operating to control tissue-specific alternative splicing of Sh 3' domains and a re discussed in terms of potential underlying mechanisms for regulatin g the tissue-specific expression of alternatively spliced genes. (C) 1 997 John Wiley & Sons, Inc.