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.
Mascarell
Laurent
L
Unité de Biologie des Populations Lymphocytaires, Institut Pasteur, 75724 Paris cedex 15, France. lmascarell@stallergenes.fr
Auger
Rodolphe
R
Kanellopoulos
Jean M
JM
Truffa-Bachi
Paolo
P
D017398:Alternative Splicing / Q000187:drug effects* / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D065095:Calcineurin Inhibitors; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation; D016678:Genome / Q000235:genetics; D007438:Introns / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D022821:RNA Splice Sites / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017385:Sequence Homology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology*
D065095:Calcineurin Inhibitors; D008565:Membrane Proteins; D020033:Protein Isoforms; D022821:RNA Splice Sites; D012333:RNA, Messenger; C424134:Sytl2 protein, mouse; D016572:Cyclosporine; D016559:Tacrolimus