Interleukin (IL) 15/IL-T production by the adult T-cell leukemia cell line HuT-102 is associated with a human T-cell lymphotrophic virus type I R region/IL-15 fusion message that lacks many upstream AUGs that normally attenuate IL-15 mRNA translation

被引:188
作者
Bamford, RN [1 ]
Battiata, AP [1 ]
Burton, JD [1 ]
Sharma, H [1 ]
Waldmann, TA [1 ]
机构
[1] GENZYME CORP,CAMBRIDGE,MA 02139
关键词
D O I
10.1073/pnas.93.7.2897
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We reported previously that the human T-cell lymphotrophic virus type I (HTLV-I)-associated adult T-cell leukemia line HuT-102 produces a cytokine designated interleukin (IL) T that requires interleukin (IL) 2 receptor beta-subunit expression for its action, Using anti-cytokine antibodies, we demonstrated that IL-T is identical to the simultaneously described IL-15, When compared to activated monocytes, IL-15 mRNA expression was 6- to 10-fold greater in HuT-102 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, Normally, by alternative splicing, this 118-nucleotide R element represents the most 5' region of several HTLV-I transcripts including tax, rex, and env, The introduction of the R element eliminated over 200 nucleotides of the IL-15 5'-UTR, including 8 of 10 upstream AUGs that are present in normal IL-15 messages, On analysis of the 5'-UTR of normal IL-15, we demonstrated that the presence of these 10 upstream AUGs interferes with IL-15 mRNA translation, Thus, IL-15 synthesis by the adult T-cell leukemia line HuT-102 involves an increase in IL-15 mRNA transcription and translation secondary to the production of an HTLV-I R element fusion message that lacks many upstream AUGs.
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页码:2897 / 2902
页数:6
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