Making sense of Dlx1 antisense RNA

Abstract

Long non-coding RNAs (lncRNAs) have been recently recognized as a major class of regulators in mammalian systems. LncRNAs function by diverse and heterogeneous mechanisms in gene regulation, and are key contributors to development, neurological disorders, and cancer. This emerging importance of lncRNAs, along with recent reports of a functional lncRNA encoded by the mouse Dlx5-Dlx6 locus, led us to interrogate the biological significance of another distal-less antisense lncRNA, the previously uncharacterized Dlx1 antisense (Dlx1as) transcript. We have functionally ablated this antisense RNA via a highly customized gene targeting approach in vivo. Mice devoid of Dlx1as RNA are viable and fertile, and display a mild skeletal and neurological phenotype reminiscent of a Dlx1 gain-of function phenotype, suggesting a role for this non-coding antisense RNA in modulating Dlx1 transcript levels and stability. The reciprocal relationship between Dlx1as and Dlx1 places this sense-antisense pair into a growing class of mammalian lncRNA-mRNA pairs characterized by inverse regulation.