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Journal of Cardiovascular Translational Research

Erschienen in:

30.03.2022 | Original Article

Functional Impact and Regulation of Alternative Splicing in Mouse Heart Development and Disease

verfasst von: Carlos Martí-Gómez, Javier Larrasa-Alonso, Marina López-Olañeta, María Villalba-Orero, Pablo García-Pavía, Fátima Sánchez-Cabo, Enrique Lara-Pezzi

Erschienen in: Journal of Cardiovascular Translational Research | Ausgabe 6/2022

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Abstract

Alternative splicing (AS) plays a major role in the generation of transcript diversity. In the heart, roles have been described for some AS variants, but the global impact and regulation of AS patterns are poorly understood. Here, we studied the AS profiles in heart disease, their relationship with heart development, and the regulatory mechanisms controlling AS dynamics in the mouse heart. We found that AS profiles characterized the different groups and that AS and gene expression changes affected independent genes and biological functions. Moreover, AS changes, specifically in heart disease, were associated with potential protein–protein interaction changes. While developmental transitions were mainly driven by the upregulation of MBNL1, AS changes in disease were driven by a complex regulatory network, where PTBP1 played a central role. Indeed, PTBP1 over-expression was sufficient to induce cardiac hypertrophy and diastolic dysfunction, potentially by perturbing AS patterns.

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Titel: Functional Impact and Regulation of Alternative Splicing in Mouse Heart Development and Disease
verfasst von: Carlos Martí-Gómez
Javier Larrasa-Alonso
Marina López-Olañeta
María Villalba-Orero
Pablo García-Pavía
Fátima Sánchez-Cabo
Enrique Lara-Pezzi
Publikationsdatum: 30.03.2022
Verlag: Springer US
Erschienen in: Journal of Cardiovascular Translational Research / Ausgabe 6/2022
Print ISSN: 1937-5387
Elektronische ISSN: 1937-5395
DOI: https://doi.org/10.1007/s12265-022-10244-x

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Functional Impact and Regulation of Alternative Splicing in Mouse Heart Development and Disease

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