The RNA-binding protein Rbm38 is dispensable during pressure overload-induced cardiac remodeling in mice

<div><p>The importance of tightly controlled alternative pre-mRNA splicing in the heart is emerging. The RNA binding protein Rbm24 has recently been identified as a pivotal cardiac splice factor, which governs sarcomerogenesis in the heart by controlling the expression of alternative protein isoforms. Rbm38, a homolog of Rbm24, has also been implicated in RNA processes such as RNA splicing, RNA stability and RNA translation, but its function in the heart is currently unknown. Here, we investigated the role of Rbm38 in the healthy and diseased adult mouse heart. In contrast to the heart- and skeletal muscle-enriched protein Rbm24, Rbm38 appears to be more broadly expressed. We generated somatic Rbm38 -/- mice and show that global loss of Rbm38 results in hematopoietic defects. Specifically, Rbm38 -/- mice were anemic and displayed enlarged spleens with extramedullary hematopoiesis, as has been shown earlier. The hearts of Rbm38 -/- mice were mildly hypertrophic, but cardiac function was not affected. Furthermore, Rbm38 deficiency did not affect cardiac remodeling (i.e. hypertrophy, LV dilation and fibrosis) or performance (i.e. fractional shortening) after pressure-overload induced by transverse aorta constriction. To further investigate molecular consequences of Rbm38 deficiency, we examined previously identified RNA stability, splicing, and translational targets of Rbm38. We found that stability targets p21 and HuR, splicing targets Mef2d and Fgfr2, and translation target p53 were not altered, suggesting that these Rbm38 targets are tissue-specific or that Rbm38 deficiency may be counteracted by a redundancy mechanism. In this regard, we found a trend towards increased Rbm24 protein expression in Rbm38 -/- hearts. Overall, we conclude that Rbm38 is critical in hematopoiesis, but does not play a critical role in the healthy and diseased heart.</p>