Bamford R N, Battiata A P, Waldmann T A
Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
J Leukoc Biol. 1996 Apr;59(4):476-80. doi: 10.1002/jlb.59.4.476.
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.
我们先前报道，人类I型嗜T细胞病毒（HTLV-I）相关的成人T细胞白血病（ATL）细胞系HuT-102产生一种名为白细胞介素（IL）-T的细胞因子。使用抗细胞因子抗体，我们证明IL-T与同时报道的IL-15相同。IL-15信息表达与IL-15合成之间不一致的观察结果促使我们检查正常和异常的IL-15 mRNA，以寻找在RNA翻译水平抑制蛋白质产生的转录后调控机制。与活化的单核细胞相比，HuT-102 T细胞中IL-15 mRNA表达高6至10倍。HuT-102的主要IL-15信息是一种嵌合mRNA，它连接了HTLV-I长末端重复序列R区域的一段和IL-15的5'非翻译区（UTR）。R片段的引入消除了IL-15 5'UTR超过200个核苷酸，包括正常IL-15信息中存在的10个上游AUG中的8个。通过对正常IL-15的5'UTR进行分析，我们证明这10个上游AUG会干扰IL-15 mRNA的翻译。因此，ATL细胞系HuT-102合成IL-15涉及IL-15 mRNA转录和翻译的增加，这是由于产生了缺乏许多上游AUG的HTLV-I-R融合信息所致。
