The long noncoding RNA Peanut promotes neurogenesis and rod photoreceptor differentiation during postnatal retinal development.

Long noncoding RNAs (lncRNAs) display pervasive expression and function in the developing nervous system. Temporal profiling of gene expression in the retina has demonstrated differential expression of lncRNAs throughout development, however determinations of lncRNA function during retinal development remain limited. In this study, we identify numerous lncRNAs with dynamic temporal expression and characterize the function of the lncRNA Gm11454, which we have named Peanut. Using an overexpression model in mice, we determine that Peanut promotes rod photoreceptor fate and neurogenesis of retinal progenitor cells (RPCs) via inhibition of Notch signaling and regulating expression of neighboring gene Tox2. A novel Peanut knockout mouse model demonstrates that Peanut is required for proper visual function and photoreceptor gene expression. Finally, we determined that Peanut is necessary for proper cell cycle progression and neurogenesis. Our results characterize the function of a novel lncRNA as a regulator of RPC neurogenesis and differentiation and support the importance of lncRNAs in the developing retina. Overall design: RNAseq profiling of Peanut heterozygote and knockout mouse retinas at P0 and P22.