文章目录

硒代半胱氨酸tRNA甲基化促进黑色素瘤转移的氧化应激抵抗

原文发布日期：2024-10-22

英文摘要：

摘要翻译：

原文链接：

文章：

硒代半胱氨酸tRNA甲基化促进黑色素瘤转移的氧化应激抵抗

Selenocysteine tRNA methylation promotes oxidative stress resistance in melanoma metastasis

原文发布日期：2024-10-22

英文摘要：

Selenocysteine-containing proteins play a central role in redox homeostasis. Their translation is a highly regulated process and is dependent on two tRNASec isodecoders differing by a single 2′-O-ribose methylation called Um34. Here we characterized FTSJ1 as the Um34 methyltransferase and show that its activity is required for efficient selenocysteine insertion at the UGA stop codon during translation. Specifically, loss of Um34 leads to ribosomal stalling and decreased UGA recoding. FTSJ1-deficient cells are more sensitive to oxidative stress and show decreased metastatic colonization in xenograft models of melanoma metastasis. We found that FTSJ1 mediates efficient translation of selenoproteins essential for the cellular antioxidant response. Our findings uncover a role for tRNASec Um34 modification in oxidative stress resistance and highlight FTSJ1 as a potential therapeutic target specific for metastatic disease.

摘要翻译：

含硒的蛋白质在氧化还原平衡中起着核心作用。它们的翻译过程高度受调控，并依赖于两个差异仅在一个2′-O-ribose甲基化位点的不同tRNASec同义子转录酶，分别称为Um34。在这里，我们表征了FTSJ1为这种甲基转移酶，并表明其活性对于在翻译过程中高效插入硒于UGA终止密码子至关重要。具体来说，缺乏Um34会导致核糖体阻塞和减少的UGA重新编码。带有FTSJ1缺陷的细胞对氧化应激更为敏感，并且在黑色素瘤移植物模型中转移癌组织的下降。我们发现，FTSJ1促进含硒蛋白的有效翻译，这些蛋白对于细胞抗氧化应激至关重要。我们的发现揭示了tRNASec Um34甲基化修改在抗氧压力抵抗中的作用，并将FTSJ1定位为一种特定针对转移性疾病潜在的治疗靶点。