SMN deficiency-induced alternative splicing dysregulation in cardiac defects - PubMed
6 hours ago
- #Spinal Muscular Atrophy
- #Alternative Splicing
- #Cardiac Defects
- Spinal muscular atrophy (SMA) is a multisystem disorder linked to reduced survival motor neuron (SMN) protein, affecting the heart.
- In SMA mice models, SMN deficiency impaired postnatal cardiac development and contractile function, reducing cardiomyocyte proliferation and increasing apoptosis.
- Alternative splicing of Mdm2 and Mdm4 was dysregulated in SMA hearts, leading to upregulation of p53 pathway targets.
- SMN deficiency disrupted spliceosomal snRNP assembly, associated with changes in SmB expression and localization, and SmB depletion replicated mis-splicing effects in cardiomyocytes.
- The findings suggest an SMN-SmB-snRNP assembly pathway connects SMN deficiency to abnormal splicing and p53 activation, offering insights into SMA cardiac pathology and potential adjunct therapies.