The smooth muscle-specific lncRNA Carmn is required for visceral smooth muscle contractile function

Altered gastrointestinal (GI) motility is associated with significant morbidity and mortality. Here, we aimed at delineating the functional role of Carmn (Cardiac mesoderm enhancer-associated noncoding RNA), a SMC-specific lncRNA, in GI motility. In this study, we observed that Carmn global knockout (gKO) or inducible smooth muscle cell-specific KO (iKO) mice exhibited premature lethality owing to colonic pseudo-obstruction, characterized by severe distension of the cecum and colon. Bulk RNA-seq and snRNA-seq of colonic muscularis showed that Carmn deficiency impairs the contraction of the colonic muscularis and disrupts the colon homeostasis, which closely related with the down-regulation of the genes maintain the SMC contraction, especially the Mylk. Overall, our data suggest that Carmn is indispensable for maintaining GI contractile function. Overall design: The colonic muscularis were isolated from Carmn KO and control mice for bulk RNA-sequecing or single-nucleus RNA-sequencing.