
We performed high-throughput RNA sequencing to analyze circular RNA profile in human cardiac disease and developed transgenic mice to explore the roles of circNlgn. Back-splicing of the neuroligin gene led to the translation of a circular RNA derived peptide with a 9-amino-acid nuclear localization motif. Nuclear translocation of Nlgn173, dysregulated expression of ING4 and C8orf44-SGK3, and immunohistochemical markers of cardiac fibrosis were detected in a panel of 145 patient specimens. Phenotypic changes observed in left ventricular pressure overload and transgenic mice were abrogated with silencing of circNlgn or its targets ING4 and SGK3. Dysregulation of this process contributes to fibrosis and heart failure in cardiac overload induced remodeling.
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