RT Journal Article
T1 Functional Impact and Regulation of Alternative Splicing in Mouse Heart Development and Disease
A1 Martí-Gómez, Carlos
A1 Larrasa-Alonso, Javier
A1 López-Olañeta, Marina
A1 Villalba Orero, María
A1 García-Pavía, Pablo
A1 Sánchez-Cabo, Fátima
A1 Lara-Pezzi, Enrique
AB 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.
PB Springer
SN 1937-5387
YR 2022
FD 2022
LK https://hdl.handle.net/20.500.14352/97926
UL https://hdl.handle.net/20.500.14352/97926
LA eng
NO Martí-Gómez, C., Larrasa-Alonso, J., López-Olañeta, M. et al. Functional Impact and Regulation of Alternative Splicing in Mouse Heart Development and Disease. J. of Cardiovasc. Trans. Res. 15, 1239–1255 (2022). https://doi.org/10.1007/s12265-022-10244-x
NO European Commission 
NO Ministerio de Economía y Competitividad (España)
NO Comunidad de Madrid
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 15 abr 2025