RNA Toxicity and Interacting RNA-Binding Protein NOVA2 of (UUUCA)exp RNA Foci in Familial Cortical Myoclonic Tremor with Epilepsy - PubMed
5 hours ago
- #NOVA2
- #RNA toxicity
- #pentanucleotide repeat expansion
- Familial cortical myoclonic tremor with epilepsy (FCMTE) is an autosomal dominant neurological disease characterized by cortical myoclonic tremor and epileptic seizures.
- The pathogenic mechanism involves a (TTTCA) pentanucleotide repeat expansion insertion, but its exact role was unclear.
- Study focused on (UUUCA)exp RNA foci formation and their toxicity in FCMTE1 patient-derived iPSC-neurons.
- (TTTCA)exp insertion did not alter SAMD12 expression or produce repeat peptides.
- (UUUCA)exp RNA foci were detected in cell lines and iPSC-neurons, showing toxic effects.
- NOVA2, a neuron-specific splicing regulator, was identified as the key RNA-binding protein interacting with (UUUCA)exp RNA.
- (UUUCA)exp RNA disrupted NOVA2's nuclear distribution, and NOVA2 knockdown promoted RNA foci formation.
- Shared synaptic-related alternative splicing pathways were observed in FCMTE1-iPSC-neurons and NOVA target genes.
- Findings suggest a repeat motif-dependent mechanism involving RNA foci and NOVA2 disruption in FCMTE pathogenesis.