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SRRM2, a potential blood biomarker revealing high alternative splicing in Parkinson's disease.
PLoS One. 2010 Feb 08; 5(2):e9104.Plos

Abstract

BACKGROUND

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.

METHODOLOGY/PRINCIPAL FINDINGS

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.

CONCLUSIONS/SIGNIFICANCE

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.

Authors+Show Affiliations

Department of Molecular and Cellular Pharmacology, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, United States of America.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20161708

Citation

Shehadeh, Lina A., et al. "SRRM2, a Potential Blood Biomarker Revealing High Alternative Splicing in Parkinson's Disease." PloS One, vol. 5, no. 2, 2010, pp. e9104.
Shehadeh LA, Yu K, Wang L, et al. SRRM2, a potential blood biomarker revealing high alternative splicing in Parkinson's disease. PLoS One. 2010;5(2):e9104.
Shehadeh, L. A., Yu, K., Wang, L., Guevara, A., Singer, C., Vance, J., & Papapetropoulos, S. (2010). SRRM2, a potential blood biomarker revealing high alternative splicing in Parkinson's disease. PloS One, 5(2), e9104. https://doi.org/10.1371/journal.pone.0009104
Shehadeh LA, et al. SRRM2, a Potential Blood Biomarker Revealing High Alternative Splicing in Parkinson's Disease. PLoS One. 2010 Feb 8;5(2):e9104. PubMed PMID: 20161708.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SRRM2, a potential blood biomarker revealing high alternative splicing in Parkinson's disease. AU - Shehadeh,Lina A, AU - Yu,Kristine, AU - Wang,Liyong, AU - Guevara,Alexandra, AU - Singer,Carlos, AU - Vance,Jeffery, AU - Papapetropoulos,Spyridon, Y1 - 2010/02/08/ PY - 2009/11/07/received PY - 2010/01/18/accepted PY - 2010/2/18/entrez PY - 2010/2/18/pubmed PY - 2010/10/1/medline SP - e9104 EP - e9104 JF - PloS one JO - PLoS One VL - 5 IS - 2 N2 - BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/20161708/SRRM2_a_potential_blood_biomarker_revealing_high_alternative_splicing_in_Parkinson's_disease_ L2 - https://dx.plos.org/10.1371/journal.pone.0009104 DB - PRIME DP - Unbound Medicine ER -