Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Department of Personalized Genomic Medicine for Health, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Cells. 2023 Dec 28;13(1):69. doi: 10.3390/cells13010069.
Recent advancements in genome analysis technology have revealed the presence of read-through transcripts in which transcription continues by skipping the polyA signal. We here identified and characterized a new read-through transcript, . With cDNA amplification from THP-1 cells, the product was successfully generated. We also generated , another isoform, by introducing point mutations. Notably, while APOE3 and APOE4 exhibited extracellular secretion, both TOMM40-APOE3 and TOMM40-APOE4 were localized exclusively to the mitochondria. But functionally, they did not affect mitochondrial membrane potential. Cell death induction studies illustrated increased cell death with TOMM40-APOE3 and TOMM40-APOE4, and we did not find any difference in cellular function between the two isoforms. These findings indicated that the new mitochondrial protein TOMM40-APOE has cell toxic ability.
近年来，基因组分析技术的进步揭示了读通转录本的存在，其中转录通过跳过 polyA 信号继续进行。我们在这里鉴定并表征了一种新的读通转录本 。通过从 THP-1 细胞中扩增 cDNA，成功生成了 产物。我们还通过引入点突变生成了另一种异构体 。值得注意的是，虽然 APOE3 和 APOE4 表现出细胞外分泌，但 TOMM40-APOE3 和 TOMM40-APOE4 都仅定位于线粒体。但是，在功能上，它们不影响线粒体膜电位。细胞死亡诱导研究表明，TOMM40-APOE3 和 TOMM40-APOE4 诱导细胞死亡增加，我们没有发现两种异构体之间在细胞功能上有任何差异。这些发现表明，新的线粒体蛋白 TOMM40-APOE 具有细胞毒性。
