Expression Landscape and Circadian Regulation of lncRNAs in the Kidney

Recent multi-omics work shows that the diurnal rhythmicity of kidney function is associated with circadian oscillations in renal mRNA, protein and metabolite abundances. Yet circadian regulation of renal lncRNAs, which are emerging as important modulators of diverse (patho)physiological processes, remains largely unexplored. Here, we provide a comprehensive characterization of renal lncRNA expression across cell types and circadian time points using bulk RNA-Seq and single-nucleus RNA-Seq (snRNA-seq) using kidney samples from male mice. Although the majority of lncRNAs are lowly expressed and only a fraction are annotated, their profiles sufficed to distinguish nearly all renal cell types. Compared with mRNAs, lncRNAs were more cell-type specific and an inverse correlation between cell-type specificity and expression level was evident. To assess the role of the circadian clock, we used mice lacking the core-clock regulator BMAL1 in renal tubules. Approximately one-sixth of lncRNAs and one-third of mRNAs were rhythmic. In contrast with mRNAs, lncRNAs exhibited an asymmetric temporal distribution between night and day, with peak expression occurring preferentially during the inactive phase of the mice. Bmal1 deletion partially disrupted rhythmicity in both biotypes and altered overall expression levels; lncRNAs were predominantly upregulated. These findings uncover the diversity of renal lncRNAs, their cellular distribution and their circadian regulation in male mice.