The melanoma antigens MELOE-1 and MELOE-2 are translated from a bona fide polycistronic mRNA containing functional IRES sequences.
The melanoma antigens MELOE-1 and MELOE-2 are translated from a bona fide polycistronic mRNA containing functional IRES sequences.
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DOI：
10.1371/journal.pone.0075233
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lang F
中科院分区：
文献类型：
--
作者：
Carbonnelle D;Vignard V;Sehedic D;Moreau-Aubry A;Florenceau L;Charpentier M;Mikulits W;Labarriere N;Lang F
我们先前对黑色素瘤抗原的研究鉴定了两种新的多肽，命名为MELOE-1和MELOE-2，它们参与免疫监视。有趣的是，这些抗原由meloe mRNA的不同开放阅读框（ORF）编码，其仅在黑素细胞谱系中显著表达。此外，MELOE-1和MELOE-2特异性T细胞克隆识别黑色素瘤细胞，但识别正常黑色素细胞非常差，这表明在正常细胞与肿瘤细胞中meloe的差异翻译。这促使我们阐明这些抗原在黑色素瘤细胞中的翻译机制。我们首先证明，没有剪接事件或隐蔽启动子可以产生较短的meloe转录只包含两个ORF之一。用与编码MELOE-2的ORF接近的siRNA触发meloe RNA降解废除了MELOE-1和MELOE-2的表达，从而证实了两个ORF总是相关的。接下来，我们显示，在双顺反子报告系统中，IRES活性可以在MELOE-1和MELOE-2的上游检测到，并最终证实了它们在具有eGFP构建体的黑素瘤细胞中从全长meloe cDNA的翻译。总之，meloe是一种多顺反子mRNA，在黑色素瘤细胞中通过IRES依赖性翻译产生MELOE-1和MELOE-2抗原，这可以解释其肿瘤特异性。
Our previous studies on melanoma antigens identified two new polypeptides, named MELOE-1 and MELOE-2, that are involved in immunosurveillance. Intriguingly, these antigens are coded by distinct open reading frames (ORF) of the meloe mRNA which is significantly expressed only in the melanocytic lineage. In addition, MELOE-1 and -2 specific T cell clones recognized melanoma cells but very poorly normal melanocytes suggesting differential translation of meloe in normal vs tumor cells. This prompted us to elucidate the mechanisms of translation of these antigens in melanoma cells. We first demonstrated that no splicing event or cryptic promoter could generate shorter meloe transcripts containing only one of the two ORFs. Triggering meloe RNA degradation with a siRNA close to the ORF coding for MELOE-2 abrogated expression of both MELOE-1 and MELOE-2, thus confirming that the two ORFs are always associated. Next we showed, in a bicistronic reporter system, that IRES activities could be detected upstream of MELOE-1 and MELOE-2 and finally confirmed their translation from full length meloe cDNA in melanoma cells with eGFP constructs. In conclusion, meloe is a polycistronic mRNA that generates both MELOE-1 and MELOE-2 antigens through IRES-dependent translation in melanoma cells and that may explain their tumor specificity.
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影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
DOI：
10.1038/nri3191
发表时间：
2012-03-22
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
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通讯作者：
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影响因子：
4.5
作者：
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通讯作者：
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影响因子：
21.3
作者：
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通讯作者：
Kageyama, Yuji
影响因子：
4.1
作者：
Jean, Didier;Rousselet, Nathalie;Frade, Raymond
通讯作者：
Frade, Raymond