Transcriptomic Alterations in Spliceosome Components in Advanced Heart Failure: Status of Cardiac-Specific Alternative Splicing Factors

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 <i>SNRPD2</i> (FC = 1.35, <i>p</i> < 0.05) and <i>DHX35</i> (FC = 1.34, <i>p</i> < 0.001) mRNA levels. In contrast, we observed generalised downregulation of the A complex and cardiac-specific AS factors, such as the multifunctional protein <i>PCBP2</i> (FC = -1.29, <i>p</i> < 0.001) and the RNA binding proteins <i>QKI</i> (FC = -1.35, <i>p</i> < 0.01). In addition, we found a relationship between <i>SNPRD2</i> (an E complex component) and the left ventricular mass index in ICM patients (r = 0.779; <i>p</i> < 0.01). On the other hand, we observed the specific underexpression of DDX46 (FC = -1.29), <i>RBM17</i> (FC = -1.33), <i>SDE2</i> (FC = -1.35) and <i>RBFOX1</i> (FC = -1.33), <i>p</i> < 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.