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

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

Young@Heart: empowering the next generation of cardiovascular researchers

In recognition of the increasing health burden of cardiovascular disease, the Dutch CardioVascular Alliance (DCVA) was founded with the ambition to lower the cardiovascular disease burden by 25% in 2030. To achieve this, the DCVA is a platform for all stakeholders in the cardiovascular field to align policies, agendas and research. An important goal of the DCVA is to guide and encourage young researchers at an early stage of their careers in order to help them overcome challenges and reach their full potential. Young@Heart is part of the DCVA that supports the young cardiovascular research community. This article illustrates the challenges and opportunities encountered by young cardiovascular researchers in the Netherlands and highlights Young@Heart’s vision to benefit from these opportunities and optimise collaborations to contribute to lowering the cardiovascular disease burden together as soon as possible. Dutch contribution to the field Dutch cardiovascular alliance (DCVA) is a platform that combines stakeholders in the cardiovascular field with the goal to lower cardiovascular disease burden by 25% in 2030. Young@Heart is part of the talent pillar of DCVA and represents young researchers in the Netherlands. Young@Heart aims to provide career perspectives in academic, corporate and non-governmental settings for talented basic and clinical scientists. By providing workshops, national and international networking and funding opportunities, Young@Heart hopes to ensure a bright future for cardiovascular research in the Netherlands

The epigenetic landscape of transgenerational acclimation to ocean warming

Epigenetic inheritance is a potential mechanism by which the environment in one generation can influence the performance of future generations1. Rapid climate change threatens the survival of many organisms; however, recent studies show that some species can adjust to climate-related stress when both parents and their offspring experience the same environmental change2,3. Whether such transgenerational acclimation could have an epigenetic basis is unknown. Here, by sequencing the liver genome, methylomes and transcriptomes of the coral reef fish, Acanthochromis polyacanthus, exposed to current day (+0 °C) or future ocean temperatures (+3 °C) for one generation, two generations and incrementally across generations, we identified 2,467 differentially methylated regions (DMRs) and 1,870 associated genes that respond to higher temperatures within and between generations. Of these genes, 193 were significantly correlated to the transgenerationally acclimating phenotypic trait, aerobic scope, with functions in insulin response, energy homeostasis, mitochondrial activity, oxygen consumption and angiogenesis. These genes may therefore play a key role in restoring performance across generations in fish exposed to increased temperatures associated with climate change. Our study is the first to demonstrate a possible association between DNA methylation and transgenerational acclimation to climate change in a vertebrate