Identification of regulatory cis-acting elements for alternative splicing of presenilin 2 exon 5 under hypoxic stress conditions
Identification of regulatory cis-acting elements for alternative splicing of presenilin 2 exon 5 under hypoxic stress conditions
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DOI：
10.1111/j.1471-4159.2004.02798.x
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发表时间：
2004-12-01
影响因子：
4.7
通讯作者：
Imaizumi, K
中科院分区：
文献类型：
--
作者：
Higashide, S;Morikawa, K;Imaizumi, K
早老素2（PS2）基因缺失外显子5（PS2 V）的选择性剪接形式在散发性阿尔茨海默病的人脑中被发现。在人神经母细胞瘤SK-N-SH细胞中，低氧应激诱导PS2 V，表明低氧应激影响PS2外显子5的剪接机制。在这里，我们确定了关键的顺式作用元件（秒2）的PS2前mRNA负责PS2外显子5在缺氧应激条件下的异常剪接。该元件由外显子5中的23个核苷酸组成，RNA结构分析显示该序列中存在茎环结构。用针对顺式作用元件的反义寡核苷酸治疗引起外显子5包涵体的增加。这些结果表明，在这项研究中确定的sec 2是一个新的调控元件的外显子5剪接在压力条件下，反式作用因子可以特异性地结合到元件跳PS2的外显子5。
An alternatively spliced form of the presenilin 2 (PS2) gene lacking exon 5 (PS2V) was found in human brains with sporadic Alzheimer's disease. PS2V was induced by hypoxic stress in human neuroblastoma SK-N-SH cells, indicating that hypoxic stress affects the splicing machineries for PS2 exon 5. Here, we identified the critical cis-acting element (sec 2) on the PS2 pre-mRNA responsible for the aberrant splicing of PS2 exon 5 under hypoxic stress conditions. The element was composed of 23 nucleotides in exon 5 and RNA structural analyses showed a stem-loop structure in this sequence. Treatment with an antisense oligonucleotide directed toward the cis-acting element caused an increase in exon 5 inclusion. These results indicate that the sec 2 identified in this study is a novel regulatory element for exon 5 splicing under stress conditions and that trans-acting factors could specifically bind to the element to skip exon 5 of PS2.