Transcriptomic Alterations in Spliceosome Components in Advanced Heart Failure: Status of Cardiac-Specific Alternative Splicing Factors.
Isaac Giménez-EscamillaLorena Pérez-CarrilloIrene González-TorrentMarta Delgado-ArijaCarlota BenedictoManuel PortolésEstefanía TarazónEsther Roselló-LletíPublished in: International journal of molecular sciences (2024)
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.
Keyphrases
- left ventricular
- heart failure
- rna seq
- gene expression
- end stage renal disease
- single cell
- chronic kidney disease
- ejection fraction
- newly diagnosed
- acute heart failure
- signaling pathway
- drug delivery
- binding protein
- magnetic resonance imaging
- atrial fibrillation
- dna methylation
- cell proliferation
- computed tomography
- hypertrophic cardiomyopathy
- acute myocardial infarction
- mitral valve
- genome wide
- patient reported outcomes
- poor prognosis
- long non coding rna
- contrast enhanced