The LncRNA Fendrr Regulates Lung Development via its Triplex Forming Site the Expression of Fibrosis Genes

Long non-coding RNAs are a very versatile class of molecules that have important roles in regulating a cells function, including regulating other genes on the transcriptional level. One of these mechanisms is that RNA can directly interact with DNA by recruiting additional components such as proteins to these sites via a RNA:dsDNA triplex formation. We genetically deleted the triplex forming sequence from the lncRNA Fendrr in mice and find that this FendrrBox is partially required for Fendrr function. we We find that the loss of the triplex forming site in developing lungs causes a dysregulation of gene programs, associated with lung fibrosis. Deregulated genes that contain a FendrrBox binding element in their promoter are regulated by Wnt signaling, together with Fendrr, implicating that Fendrr acts in concert with Wnt signaling to regulate lung fibrosis. Examination of Fendrr triplex-forming box function in vivo and ex vivo in mouse lung