Abstract 13305: Impact of Small Cajal-Body Associated RNAs in IPSC-Derived Cardiomyocytes From Progeria and Noonan Patients

Introduction: Progeria and Noonan syndrome are major genetic disorders that impact the cardiovascular system and lead to congenital heart defects in children. The small Cajal body-associated RNAs (scaRNAs) are a class of H/ACA box non-coding RNAs, which play an important role in the biochemical modification of spliceosomal RNAs and contribute to alternative splicing and maturation of mRNAs. In this study, we aim to elucidate the role of scaRNAs during cardiac differentiation and its effect in Progeria and Noonan Patients-derived induced pluripotent stem cell-derived cardiomyocytes (iCMC). Hypothesis: We hypothesize that scaRNAs have a significant role in cardiac development and are associated with cardiovascular development in disease conditions. Methods and Results: To elucidate the role of scaRNAs in Noonan and Progeria patients during cardiomyogenesis, we differentiated iCMCs from iPSCs generated from Noonan (c.1654A>G) and Progeria (c.1824 C>T) patients. The differential expression of scaRNAs was performed by qRT-PCR and the result shows that scaRNA6, scaRNA11, scaRNA14 scaRNA20, and scaRNA28 were significantly reduced in Noonan and Progeria patients iCMC compared to normal skin fibroblast (SF)-derived iCMCs and Urinary epithelial cells (UE)-derived iCMC (Fig.1). The mRNA expression of the cardiac-specific gene in Progeria and Noonan patient-derived iCMC was significantly reduced when compared with normal iCMC. Furthermore, the scaRNA overexpressed normal iCMCs (scaRNA20-OE-iCMCs) showed significantly increased cardiac-specific mRNA and protein expressions when compared with control iCMC (Figs.2 & 3) . Conclusion: Our finding indicates that scaRNAs have major impacts on Noonan and Progeria patient-derived iCMC. Targeting the scaRNAs will have efficient therapeutic potential for Noonan and Progeria patients.