The usage of alternative splice sites in mus musculus synaptotagmin-like 2 gene is modulated by cyclosporin A and FK506 in T-lymphocytes

Cyclosporin-A and FK506 block the calcineurin activity preventing the transcription of genes sharing NFAT-like binding sequences in their promoter region. We presently show that activation of murine T-cells in presence of these immunosuppressors results in the up-regulation of the synaptotagmin-like 2 gene. However, of the four known isoforms, only mRNAs encoding the a and b isoforms accumulate. Two previously undected isoforms, each characterized by the retention of an intron, were found. The first, Slp2-e, includes exon 8, intron 8 and exon 9. The second, Slp2-f, is composed of exon 7, intron 7 and exon 8. Slp2-f has an open reading frame coding for a putative protein of 1229 amino acids sharing 47% identities with the human breast-associated antigen, SGA-72 M. In addition to the well-documented modulation of gene transcription, the two immunosuppressors also play a role in the choice of alternative splice sites on murine Slp2 pre-mRNA.