title: Brief naturalistic stress induces an alternative splice variant of SMG-1 lacking exon 63 in peripheral leukocytes.
abstract: 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.
authors: Department of Stress Science, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
authors: Ken
authors: K
authors: Kurokawa
authors: Yuki
authors: Y
authors: Kuwano
authors: Kumiko
authors: K
authors: Tominaga
authors: Tomoko
authors: T
authors: Kawai
authors: Sakurako
authors: S
authors: Katsuura
authors: Naoko
authors: N
authors: Yamagishi
authors: Yuzuru
authors: Y
authors: Satake
authors: Keisuke
authors: K
authors: Kajita
authors: Toshihito
authors: T
authors: Tanahashi
authors: Kazuhito
authors: K
authors: Rokutan
mesh_terms: D017398:Alternative Splicing / Q000502:physiology*; D000704:Analysis of Variance; D005091:Exons / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D011569:Psychiatric Status Rating Scales; D027544:Salvia / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D006854:Hydrocortisone; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; C514704:SMG1 protein, human