IL-2 REGULATES THE EXPRESSION OF THE NK-TR GENE VIA AN ALTERNATE RNA SPLICING MECHANISM

We have recently isolated and characterized human and mouse genes of a putative natural killer (NK) cell tumour-recognition protein (NK-TR) that is specifically expressed in NK cells. This gene codes for a 150 kD protein with a cyclophilin-related amino terminus followed by several positively charged domains. We report here the discovery of two sites of alternate splicing in the 5' region of the NK-TR mRNA. One of these events caused a frameshift in the open reading frame by splicing in a 28 bp exon within the cyclophilin coding region, resulting in the premature termination of the NK-TR protein. The second alternate splice stemmed from the use of an internal splice acceptor within an exon, producing a deletion of 25 amino acids in the NK-TR protein. The activation of NK cells by IL-2 produced a change in the splicing pattern that resulted in increased production of mRNAs capable of producing the complete NK-TR protein.