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.
Bamford
R N
RN
Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Battiata
A P
AP
Waldmann
T A
TA
D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D019409:Interleukin-15; D007378:Interleukins / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D014176:Protein Biosynthesis / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism / Q000502:physiology; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000502:physiology
C508024:IL15RA protein, human; C508025:Il15ra protein, mouse; D019409:Interleukin-15; D007378:Interleukins; D012333:RNA, Messenger; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2