The pervasive transcription of much of the non-coding genome during development raises the question of its functional role in regulating cell fate, tissue morphogenesis and organ function. Long intergenic non-coding RNAs (lincRNAs) are particularly useful for addressing this question, and while some have indeed been implicated in differentiation, in vivo evidence remains patchy. Now, Benoit Bruneau and colleagues address the role of lincRNAs in mouse heart development. By using computational criteria based on genomic position, epigenetic regulation and expression in in vitro cardiac differentiation protocols, the authors identify nine conserved lincRNAs, some of which are in the vicinity of and co-transcribed with known cardiac genes. Six of these lincRNAs show dynamic spatiotemporal expression patterns in the developing heart, and knockouts (generated with pronuclear Cas9 mRNA and tru-sgRNA injections) lead to changes in the expression of nearby genes in four cases. However, none of these six knockouts affect viability or fertility. Furthermore, two lincRNAs expressed in adult hearts play no role in the physiological stress response, although the Rubie lincRNA did show genetic interactions with the nearby Bmp4 gene in cardiac morphogenesis, albeit modestly. Thus, lincRNAs do not appear to have important roles in heart development in the mouse.
