Making sense of Dlx1 antisense RNA

Long non-coding RNAs (IncRNAs) 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 IncRNAs, along with recent reports of a functional IncRNA encoded by the mouse Dlx5-Dlx6 locus, led us to interrogate the biological significance of another distal-less antisense IncRNA, the previously uncharacterized Dlx1 antisense (Dlx1 as) transcript. We have functionally ablated this antisense RNA via a highly customized gene targeting approach in vivo. Mice devoid of Dlx1 as 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 Dlx1 as and Dlx1 places this sense-antisense pair into a growing class of mammalian IncRNA-mRNA pairs characterized by inverse regulation. (C) 2013 Elsevier Inc. All rights reserved.