Discovery of an evolutionarily conserved smooth muscle cell-specific lncRNACARMN

Abstract

AbstractDifferentiated vascular smooth muscle cells (VSMCs) are critical in maintaining vascular homeostasis by expressing a unique repertoire of contractile genes. Despite the well-defined coding transcriptome in differentiated VSMCs, little is known about the non-coding gene expression signature. Herein, by de novo analyzing publicly available RNA-seq and single cell RNA-seq datasets generated from different tissues and cell types, we unambiguously identifiedCARMN(CARdiac Mesoderm Enhancer-associated Non-coding RNA) as an evolutionarily conserved, SMC-specific lncRNA.CARMNwas initially annotated as the host gene ofMIR143/145cluster and recently reported to play roles in cardiac differentiation. Here, we generated aCarmnGFP knock-in reporter mouse model and confirmed its specific expression in SMCsin vivo. In addition, we foundCarmnis transcribed independently fromMir143/145and only expressed transiently in embryonic cardiomyocytes and thereafter becomes restricted to adult SMCs in both human and mouse. Furthermore, we demonstrated thatCARMNexpression is not only dramatically decreased in human vascular diseases but functionally critical in maintaining VSMC contractile phenotypein vitro. In conclusion, we provided the first evidence showing thatCARMNis an evolutionarily conserved SMC-specific lncRNA, down-regulated in different human vascular diseases, and a key lncRNA for maintaining SMC contractile phenotype.