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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Heart failure (HF) is associated with global changes in gene expression. Alternative mRNA splicing (AS) is a key regulatory mechanism underlying these changes. However, the whole status of molecules involved in the splicing process in human HF is unknown. Therefore, we analysed the spliceosome transcriptome in cardiac tissue (n = 36) from control subjects and HF patients (with ischaemic (ICM) and dilated (DCM) cardiomyopathies) using RNA-seq. We found greater deregulation of spliceosome machinery in ICM. Specifically, we showed widespread upregulation of the E and C complex components, highlighting an increase in SNRPD2 (FC = 1.35, p < 0.05) and DHX35 (FC = 1.34, p < 0.001) mRNA levels. In contrast, we observed generalised downregulation of the A complex and cardiac-specific AS factors, such as the multifunctional protein PCBP2 (FC = −1.29, p < 0.001) and the RNA binding proteins QKI (FC = −1.35, p < 0.01). In addition, we found a relationship between SNPRD2 (an E complex component) and the left ventricular mass index in ICM patients (r = 0.779; p < 0.01). On the other hand, we observed the specific underexpression of DDX46 (FC = −1.29), RBM17 (FC = −1.33), SDE2 (FC = −1.35) and RBFOX1 (FC = −1.33), p < 0.05, in DCM patients. Therefore, these aetiology-related alterations may indicate the differential involvement of the splicing process in the development of ICM and DCM.

Details

Title
Transcriptomic Alterations in Spliceosome Components in Advanced Heart Failure: Status of Cardiac-Specific Alternative Splicing Factors
Author
Giménez-Escamilla, Isaac 1   VIAFID ORCID Logo  ; Pérez-Carrillo, Lorena 1 ; González-Torrent, Irene 2 ; Delgado-Arija, Marta 1 ; Benedicto, Carlota 2 ; Portolés, Manuel 1   VIAFID ORCID Logo  ; Tarazón, Estefanía 1   VIAFID ORCID Logo  ; Roselló-Lletí, Esther 1 

 Clinical and Translational Research in Cardiology Unit, Health Research Institute Hospital La Fe (IIS La Fe), Avd. Fernando Abril Martorell 106, 46026 Valencia, Spain; [email protected] (I.G.-E.); [email protected] (L.P.-C.); [email protected] (I.G.-T.); [email protected] (M.D.-A.); [email protected] (C.B.); [email protected] (M.P.); Center for Biomedical Research Network on Cardiovascular Diseases (CIBERCV), Avd. Monforte de Lemos 3-5, 28029 Madrid, Spain 
 Clinical and Translational Research in Cardiology Unit, Health Research Institute Hospital La Fe (IIS La Fe), Avd. Fernando Abril Martorell 106, 46026 Valencia, Spain; [email protected] (I.G.-E.); [email protected] (L.P.-C.); [email protected] (I.G.-T.); [email protected] (M.D.-A.); [email protected] (C.B.); [email protected] (M.P.) 
First page
9590
Publication year
2024
Publication date
2024
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3104121099
Copyright
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.