LncRNA RUS shapes the gene expression program towards neurogenesis

Abstract

The evolution of brain complexity correlates with an increased expression of long, noncoding (lnc) RNAs in neural tissues. Although prominent examples illustrate the potential of lncRNAs to scaffold and target epigenetic regulators to chromatin loci, only few cases have been described to function during brain development. We present a first functional characterization of the lncRNA LINC01322, which we term RUS for “RNA upstream of Slitrk3.” The RUS gene is well conserved in mammals by sequence and synteny next to the neurodevelopmental gene Slitrk3. RUS is exclusively expressed in neural cells and its expression increases during neuronal differentiation of mouse embryonic cortical neural stem cells. Depletion of RUS locks neuronal precursors in an intermediate state towards neuronal differentiation resulting in arrested cell cycle and increased apoptosis. RUS associates with chromatin in the vicinity of genes involved in neurogenesis, most of which change their expression upon RUS depletion. The identification of a range of epigenetic regulators as specific RUS interactors suggests that the lncRNA may mediate gene activation and repression in a highly context-dependent manner.

Endogenous neural stem cells characterization using omics approaches: Current knowledge in health and disease

“…Such results are in line with transcriptomic data that, upon RUS depletion, show reduced expression of proliferative markers as well as neuronal differentiation genes, while pro-apoptotic and cell death genes were found to increase. Altogether, these studies highlight that lncRNAs are crucial regulators of brain cell development (Schneider et al, 2022 ).…”

“…The Pnky gene is localized near the pro-neural TF Pou3f2, and although its deletion does not affect Pou3f2 expression, it leads to loss of proliferation and decreased cortical neurogenesis. Another lncRNA named RUS, located upstream of the transmembrane protein Slitrk3 is involved in neurite outgrowth by regulating in cis this nearest upstream gene (Aruga et al, 2003 ; Schneider et al, 2022 ). However, upon RUS silencing, not only Slitrk3 expression was found downregulated, but also Notch- and Shh-related genes were affected.…”