Abstract
Abstract P3051: Master Splicing Regulator Rbpms2 Is Not Required For Murine Cardiac Development Or Contractile Function
Circulation research, Vol.133(Suppl_1)
08/04/2023
DOI: 10.1161/res.133.suppl_1.P3051
Abstract
Abstract only Post-transcriptional gene regulation (PTGR) through RNA-binding proteins (RBP) is an understudied area of cardiac biology. Emerging research describes important roles for Rbpms and Rbpms2 in RNA splicing, cardiomyocyte diploidy and proliferation, cytoskeletal reorganization and translation initiation during cardiomyocyte differentiation and cardiac development. However, the role of Rbpms2 in adult heart is largely unknown. We identified Rbpms2 as a cardiovascular-enriched RBP that is consistently downregulated in failing hearts from humans and mice. Though prior research has focused on roles in splicing, a large portion Rbpms2 protein is extranuclear, and >35% of empirically determined Rbpms binding sites localize in 3’UTRs, suggesting alternative PTGR roles. To assess Rbpms2’s role in cardiomyocyte PTGR, we assessed mRNA-seq changes in neonatal rat cardiomyocytes after overexpression and knockdown of Rbpms2. Pathway analyses revealed significant upregulation of genes involved in cell cycle control, and downregulation of genes involved in viral host defense pathway after Rbpms2 knockdown. We next characterized Rbpms2 knockout (KO) mice, which are viable without overt phenotypes, to provide initial descriptions of adult mouse cardiac function after Rbpms2 deletion. Baseline echocardiography data of male mice at 6 months of age shows normal cardiac size, structure, and function without significant difference between KO and wildtype (WT) mice (n=10). To assess the role of Rbpms2 in cardiac hypertrophy, we induced pressure overload via transverse aortic constriction (TAC) on mix-sex WT and Rbpms2-KO mice, which resulted in robust hypertrophic responses and reduced ejection fraction in both groups, but no significant differences between WT and KO mice (n=11 female, n=7-10 male). Overall, our findings are surprising given recently published data showing that Rbpms2 is a master regulator of RNA splicing affecting sarcomere organization and cardiomyocyte contractile function in zebrafish and stem cell-derived cardiomyocytes, supporting the need for follow-up studies on cardiac Rbpms2. It is possible that Rbpms compensates for the loss of Rbpms2 in the mouse heart and would require double KOs to assess synergistic phenotypes.
Details
- Title: Subtitle
- Abstract P3051: Master Splicing Regulator Rbpms2 Is Not Required For Murine Cardiac Development Or Contractile Function
- Creators
- Jared M McLendon - University of IowaXiaoming Zhang - University of IowaRyan L Boudreau - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Circulation research, Vol.133(Suppl_1)
- DOI
- 10.1161/res.133.suppl_1.P3051
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 08/04/2023
- Academic Unit
- Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984479555402771
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