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The Journal of Immunology, 1998, 160: 4418-4426.
Copyright © 1998 by The American Association of Immunologists

The 5' Untranslated Region, Signal Peptide, and the Coding Sequence of the Carboxyl Terminus of IL-15 Participate in Its Multifaceted Translational Control1

Richard N. Bamford2, Andrew P. DeFilippis, Nazli Azimi, Gloria Kurys and Thomas A. Waldmann

Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892

We previously reported that the AUG-burdened 5' untranslated region (UTR) of IL-15 mRNA impedes its translation. Here we demonstrate that the nucleotide or protein sequences of the IL-15 signal peptide and carboxyl terminus also contribute to the poor translation of IL-15 transcripts. In particular, the exchange of the IL-15 signal peptide coding sequence with that of IL-2 increased cellular and secreted levels of IL-15 protein 15- to 20-fold in COS cells, while IL-2 transcripts with the IL-15 signal peptide generated 30- to 50-fold less IL-2 protein than wild-type IL-2. Furthermore, the addition of an artificial epitope tag to the 3' coding sequence of IL-15 increased its protein production 5- to 10-fold. Combining these two IL-15 message modifications, in addition to removing the 5' UTR, increased IL-15 synthesis 250-fold compared with a wild-type construct with an intact 5' UTR. These data suggest that IL-15 mRNA, unlike IL-2 mRNA, may exist in translationally inactive pools. By storing translationally quiescent IL-15 mRNA, cells might respond to intracellular infections or other stimuli by rapidly transforming IL-15 message into one that can be efficiently translated.




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