IL-15: the role of translational regulation in their expression

We previously reported that the human T cell lymphotropic virus type I (HTLV-I)-associated adult T cell leukemia (ATL) line HuT-102 produces a cytokine designated interleukin (IL)-T. Using anti-cytokine antibodies we demonstrated that IL-T is identical to the simultaneously described IL-15. The observation of a discordance between IL-15 message expression and IL-15 synthesis led us to examine normal and aberrant IL-15 mRNA for post-transcriptional controls that inhibit protein production at the level of RNA translation. When compared to activated monocytes, IL-15 mRNA expression was 6- to 10-fold greater in HuT-102 T cells. The predominant IL-15 message from HuT-102 is a chimeric mRNA joining a segment of the R region of the long terminal repeat of HTLV-I and the 5' untranslated region (UTR) of IL-15. R segment introduction eliminated over 200 nucleotides of IL-15 5' UTR including 8 of 10 upstream AUGs that are present in the normal IL-15 message. On analysis of the 5' UTR of normal IL-15, we demonstrated that these 10 upstream AUGs interfere with IL-15 mRNA translation. Thus, IL-15 synthesis by the ATL cell line HuT-102 involves an increase in IL-15 mRNA transcription and translation secondary to the production of an HTLV-I-R fusion message that lacks many upstream AUGs.