Abstract
Abstract 20109: The RNA Binding Protein RBPMS2 is a Novel Regulator of Cardiac Stress
Circulation (New York, N.Y.), Vol.134(Suppl_1 Suppl 1), pp.A20109-A20109
11/11/2016
Abstract
IntroductionCardiac stress causes detrimental changes in gene expression. RNA binding proteins (RBPs) contribute significantly to post-transcriptional regulation of gene expression; however, few studies have evaluated RBPs in cardiac stress. To address this deficit, we aim to use bioinformatics to identify cardiac-enriched RBPs with altered expression in human failing hearts, and then characterize their roles in cardiac biology and disease.ResultsUsing publicly-available human transcriptional profiling data, we found that RBPMS2 mRNA is highly enriched in human heart (>20-fold relative to other tissues), and consistently downregulated in failing myocardium (>30% in 7 of 9 independent heart failure patient cohorts). Although RBPMS2 is a known regulator of smooth muscle cell plasticity, its function in cardiomyocytes is unknown. Using cell fractionation and QPCR, we found that the majority of RBPMS2 mRNA in mouse hearts derives from cardiomyocytes (>55%). Subsequent studies in cultured cardiomyocytes showed that RBPMS2-GFP fusion proteins heterogeneously distribute in cytosolic and nuclear compartments, but distinctly shift to stress granules upon treatment with chemical inducers of oxidative stress. In addition, we found that RBPMS2 mRNAs are upregulated in phenylephrine-treated cardiomyocytes (1.4-fold, p=0.05), and surprisingly, forced overexpression of RBPMS2 blunted hypertrophy-induced increases in protein synthesis (Figure 1). Further evidence for an anti-hypertrophic effect was observed in vivo, as cardiac-targeted RBPMS2 overexpression using AAV9 led to decreased heart size within 10 weeks.ConclusionThese results support that RBPMS2 is an important cardiomyocyte RNA binding protein that responds to stress and modifies hypertrophic growth processes. Future work in experimental models of heart disease will define the specific role of RBPMS2 as a post transcriptional regulator of gene expression during cardiac stress.
Details
- Title: Subtitle
- Abstract 20109: The RNA Binding Protein RBPMS2 is a Novel Regulator of Cardiac Stress
- Creators
- Jared McLendon - Dept of Internal Medicine, Univ of Iowa -- Carver College of Medicine, Iowa City, IAXiaoming ZhangRyan Boudreau
- Resource Type
- Abstract
- Publication Details
- Circulation (New York, N.Y.), Vol.134(Suppl_1 Suppl 1), pp.A20109-A20109
- Publisher
- by the American College of Cardiology Foundation and the American Heart Association, Inc
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Language
- English
- Date published
- 11/11/2016
- Academic Unit
- Internal Medicine; Iowa Neuroscience Institute; Cardiovascular Medicine
- Record Identifier
- 9984071631002771
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