Novel IL-15 isoforms generated by alternative splicing are expressed in the intestinal epithelium.
Previous studies have identified mRNA three isoforms encoding interleukin-15 (IL-15) that are produced through differential splicing and encode for the same mature IL-15 protein with two different signal peptides. Our analysis of mouse intestinal epithelial cells revealed two new IL-15 mRNA isoforms generated by different alternative splicing events. In one form (IL-15DeltaE6), exon 6 is absent, and in the second form the first 48 nt of exon 7 are absent (IL-15DeltaE7) through usage of an alternative 5' splicing site within exon 7. These mRNA isoforms encoded in-frame IL-15 protein variants lacking either 15aa (IL-15DeltaE6) or 16aa (IL-15DeltaE7) both utilizing the normal long signal peptide. Significant structural changes were predicted for these new IL-15 isoforms. RNAse protection assays revealed the highest expression of isoform mRNA in the intestinal epithelium and functional analysis of recombinant IL-15 isoform proteins suggested possible regulatory functions.
Tan
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Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030-1319, USA.
Lefrançois
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D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D018076:DNA, Complementary; D004220:Disulfides / Q000737:chemistry; D005091:Exons; D014644:Genetic Variation; D019409:Interleukin-15 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D018807:Polymorphism, Single-Stranded Conformational; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021382:Protein Sorting Signals; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D018076:DNA, Complementary; D004220:Disulfides; D019409:Interleukin-15; D020033:Protein Isoforms; D021382:Protein Sorting Signals; D012333:RNA, Messenger; D011994:Recombinant Proteins