SRRM2, a potential blood biomarker revealing high alternative splicing in Parkinson's disease.
SRRM2, a potential blood biomarker revealing high alternative splicing in Parkinson's disease.
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DOI：
10.1371/journal.pone.0009104
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发表时间：
2010-02-08
期刊：
影响因子：
3.7
通讯作者：
Papapetropoulos S
中科院分区：
文献类型：
--
作者：
Shehadeh LA;Yu K;Wang L;Guevara A;Singer C;Vance J;Papapetropoulos S
帕金森病（PD）是一种进行性神经退行性疾病，影响全世界约500万人。诊断仍然是临床的，基于表型模式。迫切需要发现实验室标志物，以提高诊断准确性，允许临床前检测和跟踪疾病进展。这些生物标志物可以包括具有不同同种型的转录物。我们对GEO提供的3个PD微阵列实验进行了广泛的分析，发现RNA剪接基因SRRM 2（或SRm 300），丝氨酸/精氨酸重复矩阵2，是所有三个PD实验中唯一差异上调的基因。与健康对照组相比，其他神经系统疾病患者的血液中SRRM 2表达没有变化。使用实时PCR，我们报告说，较短的转录SRRM 2是1.7倍（p = 0.008）上调黑质的PD与对照组，而较长的转录下调黑质（p = 0.03）和杏仁核（p = 0.003）。 为了验证我们的结果并测试PD中选择性剪接的可能性，我们使用AffyteTM Exon_ST1阵列对28名个体（17名PD和11名对照）的外周血进行了独立的微阵列扫描，发现SRRM 2上游（5′）外显子的显著上调和下游外显子的下调，导致长亚型的共0.7倍下调（p = 0.04）。 此外，我们报告了新的信息，数百个基因与显着的选择性剪接（差异外显子表达）在PD血液与对照。RNA剪接因子SRRM 2在两种不同的PD神经元来源和PD血液中的一致失调，但在其他神经系统疾病患者的血液中没有，这使得SRRM 2成为PD的强有力的候选基因，并引起人们对RNA剪接在疾病中的作用的关注。
Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects about five million people worldwide. Diagnosis remains clinical, based on phenotypic patterns. The discovery of laboratory markers that will enhance diagnostic accuracy, allow pre-clinical detection and tracking of disease progression is critically needed. These biomarkers may include transcripts with different isoforms. We performed extensive analysis on 3 PD microarray experiments available through GEO and found that the RNA splicing gene SRRM2 (or SRm300), sereine/arginine repetitive matrix 2, was the only gene differentially upregulated among all the three PD experiments. SRRM2 expression was not changed in the blood of other neurological diseased patients versus the healthy controls. Using real-time PCR, we report that the shorter transcript of SRRM2 was 1.7 fold (p = 0.008) upregulated in the substantia nigra of PDs vs controls while the longer transcript was 0.4 downregulated in both the substantia nigra (p = 0.03) and amygdala (p = 0.003). To validate our results and test for the possibility of alternative splicing in PD, we performed independent microarray scans, using Affymetrix Exon_ST1 arrays, from peripheral blood of 28 individuals (17 PDs and 11 Ctrls) and found a significant upregulation of the upstream (5′) exons of SRRM2 and a downregulation of the downstream exons, causing a total of 0.7 fold down regulation (p = 0.04) of the long isoform. In addition, we report novel information about hundreds of genes with significant alternative splicing (differential exonic expression) in PD blood versus controls. The consistent dysregulation of the RNA splicing factor SRRM2 in two different PD neuronal sources and in PD blood but not in blood of other neurologically diseased patients makes SRRM2 a strong candidate gene for PD and draws attention to the role of RNA splicing in the disease.
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影响因子：
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作者：
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