Translational efficiency is up-regulated by alternative exon in murine IL-15 mRNA.
IL-15 promotes the growth of T cells and shares properties of IL-2. IL-2 is produced exclusively by T cells, while IL-15 message is expressed by a variety of tissues. However, it has been difficult to demonstrate IL-15 in the supernatants of many cells that express message for this cytokine. This suggests that IL-15 production is regulated by post-transcriptional controls. In this study, we cloned three types of murine IL-15 cDNA isoforms generated by alternative splicing and compared the translational efficiency among these isoforms. The translational efficiency of isoforms with alternative exon 5 containing another 3' splice site was significantly higher than that of IL-15 cDNA with originally described exon 5, which is generated by internal splicing of alternative exon 5. The translation product of the isoform containing alternative exon 5 has a shorter open reading frame due to stop codons in additional sequence, followed by a new AUG codon, and displays a shorter leader sequence. The shorter isoform of the IL-15 was detected in peritoneal macrophages stimulated with IFN-gamma and LPS, which expressed an abundant level of alternative exon 5. These results suggest that normal IL-15 production in stimulated macrophages is regulated by splicing of alternative exon 5.
Nishimura
H
H
Laboratory of Host Defense and Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Japan.
Washizu
J
J
Nakamura
N
N
Enomoto
A
A
Yoshikai
Y
Y
D017398:Alternative Splicing / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D005091:Exons / Q000276:immunology*; D019409:Interleukin-15 / Q000235:genetics* / Q000302:isolation & purification; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000235:genetics; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis / Q000276:immunology*; D012333:RNA, Messenger / Q000276:immunology*; D014158:Transcription, Genetic / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
D018076:DNA, Complementary; D019409:Interleukin-15; D008070:Lipopolysaccharides; D012333:RNA, Messenger