Brief naturalistic stress induces an alternative splice variant of SMG-1 lacking exon 63 in peripheral leukocytes
Brief naturalistic stress induces an alternative splice variant of SMG-1 lacking exon 63 in peripheral leukocytes
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DOI：
10.1016/j.neulet.2010.08.031
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发表时间：
2010-10
影响因子：
2.5
通讯作者：
Ken Kurokawa;Y. Kuwano;K. Tominaga;T. Kawai;Sakurako Katsuura;N. Yamagishi;Yuzuru Satake;Keisuke Kajita;T. Tanahashi;K. Rokutan
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文献类型：
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作者：
Ken Kurokawa;Y. Kuwano;K. Tominaga;T. Kawai;Sakurako Katsuura;N. Yamagishi;Yuzuru Satake;Keisuke Kajita;T. Tanahashi;K. Rokutan
选择性剪接（alternative splicing，AS）不仅能调节基因表达，而且在应激条件下产生具有独特性质的蛋白质异构体。然而，急性心理应激引发的AS事件尚未在人类研究中记录。在评估28名四年级医学生的唾液皮质醇水平和焦虑的变化7周前，1天前，之后立即，1周后，考试的推广，我们选择了5名男生，谁表现出典型的应激反应，并筛选AS事件在他们的循环白细胞使用基因芯片人类外显子1.0 ST阵列。27个剪接指数>1.0的基因的AS事件可以在检查后即刻和检查前7周、检查前1天或检查后1周之间检测到。在27个pre-mRNAs中，有21个发生了外显子跳跃，其中8个发生了3′UTR跳跃。在候选基因中，实时逆转录PCR验证了SMG-1外显子63的应激启动跳跃，SMG-1编码一种磷脂酰肌醇3-激酶相关蛋白激酶，对激活p53依赖性途径和无义介导的mRNA衰变至关重要。我们的研究结果表明，短暂的自然应激对AS介导的外周血白细胞基因表达调控的显着影响，并建议SMG-1剪接变异体作为急性心理应激的潜在生物标志物。
Alternative splicing (AS) not only regulates the gene expression program in response to surrounding environment, but also produces protein isoforms with unique properties under stressful conditions. However, acute psychological stress-initiated AS events have not been documented in human studies. After assessments of changes in salivary cortisol levels and anxiety among 28 fourth-grade medical students 7 weeks prior to, 1 day before, immediately after, and 1 week after an examination for promotion, we selected 5 male students, who showed a typical stress response, and screened AS events in their circulating leukocytes using the GeneChip human exon 1.0 ST array. AS events of 27 genes with splicing indices >1.0 could be detected between immediately after and either 7 weeks before, 1 day before, or 1 week after the examination. The examination stress preferentially caused skipping rather than inclusion: 21 out of the 27 pre-mRNAs underwent skipping of exons, and skipping in 3′UTR was observed in 8 genes. Among the candidate genes, real-time reverse transcription PCR validated the stress-initiated skipping of exon 63 of SMG-1 that encodes a phosphatidylinositol 3-kinase-related protein kinase crucial for activations of p53-dependent pathways and nonsense-mediated mRNA decay. Our results indicate a significant impact of brief naturalistic stressors on AS-mediated regulation of gene expression in peripheral leukocytes, and suggest the SMG-1 splice variant as a potential biomarker for acute psychological stress.