Functions of RNA-Binding Proteins in Cardiovascular Disease

Ruffenach, Grégoire; Medzikovic, Lejla; Sun, Wasila; Hong, Jason; Eghbali, Mansoureh

doi:10.3390/cells12242794

Cited by 4 publications

(2 citation statements)

References 92 publications

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“…Loss or the dysregulated activity of several RBPs have been closely associated with cardiomyopathies in humans or in animal models, as exemplified by RBM20 mutations in DCM patients [ 13 ]. With the expanded identification of the cardiac-specific RBPome, the contribution of RBP-mediated post-transcriptional regulation of cardiac-specific gene expression networks has gained considerable interest for better understanding the complexity of heart development and function [ 22 , 23 , 24 , 25 , 26 ]. Importantly, correcting pathogenic mutations in RBPs or manipulating their activity has the strong potential to rescue cardiomyopathy or promote cardiac regeneration after myocardial injury [ 27 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

RNA-Binding Proteins in Cardiomyopathies

Shi

2024

JCDD

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The post-transcriptional regulation of gene expression plays an important role in heart development and disease. Cardiac-specific alternative splicing, mediated by RNA-binding proteins, orchestrates the isoform switching of proteins that are essential for cardiomyocyte organization and contraction. Dysfunctions of RNA-binding proteins impair heart development and cause the main types of cardiomyopathies, which represent a heterogenous group of abnormalities that severely affect heart structure and function. In particular, mutations of RBM20 and RBFOX2 are associated with dilated cardiomyopathy, hypertrophic cardiomyopathy, or hypoplastic left heart syndrome. Functional analyses in different animal models also suggest possible roles for other RNA-binding proteins in cardiomyopathies because of their involvement in organizing cardiac gene programming. Recent studies have provided significant insights into the causal relationship between RNA-binding proteins and cardiovascular diseases. They also show the potential of correcting pathogenic mutations in RNA-binding proteins to rescue cardiomyopathy or promote cardiac regeneration. Therefore, RNA-binding proteins have emerged as promising targets for therapeutic interventions for cardiovascular dysfunction. The challenge remains to decipher how they coordinately regulate the temporal and spatial expression of target genes to ensure heart function and homeostasis. This review discusses recent advances in understanding the implications of several well-characterized RNA-binding proteins in cardiomyopathies, with the aim of identifying research gaps to promote further investigation in this field.

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Section: Introductionmentioning

confidence: 99%

RNA-Binding Proteins in Cardiomyopathies

Shi

2024

JCDD

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“…An increase in HuR expression in mouse cardiomyocytes has been observed during ischemia and reperfusion injury, where it has been shown to stabilize beclin mRNA, which leads to increased cell death. 7 Therefore, the role of HuR in cardiomyocyte and endothelial cell function in the context of cardiac fibrosis requires further investigation. Also, inflammation and cardiac tissue injury are closely associated, and previous studies have reported that HuR can up-regulate the expression of proinflammatory cytokines, including tumor necrosis factor α, 8 and increase the recruitment of macrophages in the injured heart.…”

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Human Antigen R, a Myofibroblast-Specific Target in Treating Cardiac Fibrosis

Srivastava,

Dhingra

2024

JACC: Basic to Translational Science

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Unraveling the Bivalent and Rapid Interactions Between a Multivalent RNA Recognition Motif and RNA: A Kinetic Approach

Pérez-Ropero,

Pérez-Ràfols,

Martelli

et al. 2024

Biochemistry

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The kinetics of the interaction between Musashi-1 (MSI1) and RNA have been characterized using surface plasmon resonance biosensor analysis. Truncated variants of human MSI1 encompassing the two homologous RNA recognition motifs (RRM1 and RRM2) in tandem (aa 1–200), and the two RRMs in isolation (aa 1–103 and aa 104–200, respectively) were produced. The proteins were injected over sensor surfaces with immobilized RNA, varying in sequence and length, and with one or two RRM binding motifs. The interactions of the individual RRMs with all RNA variants were well described by a 1:1 interaction model. The interaction between the MSI1 variant encompassing both RRM motifs was bivalent and rapid for all RNA variants. Due to difficulties in fitting this complex data using standard procedures, we devised a new method to quantify the interactions. It revealed that two RRMs in tandem resulted in a significantly longer residence time than a single RRM. It also showed that RNA with double UAG binding motifs and potential hairpin structures forms less stable bivalent complexes with MSI1 than the single UAG motif containing linear RNA. Substituting the UAG binding motif with a CAG sequence resulted in a reduction of the affinity of the individual RRMs, but for MSI1, this reduction was strongly enhanced, demonstrating the importance of bivalency for specificity. This study has provided new insights into the interaction between MSI1 and RNA and an understanding of how individual domains contribute to the overall interaction. It provides an explanation for why many RNA-binding proteins contain dual RRMs.

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Functions of RNA-Binding Proteins in Cardiovascular Disease

Cited by 4 publications

References 92 publications

RNA-Binding Proteins in Cardiomyopathies

RNA-Binding Proteins in Cardiomyopathies

Human Antigen R, a Myofibroblast-Specific Target in Treating Cardiac Fibrosis

Unraveling the Bivalent and Rapid Interactions Between a Multivalent RNA Recognition Motif and RNA: A Kinetic Approach

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