The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator.

By Jianchi Feng, Chunming Bi, Brian S. Clark, R. Mady, Palak Shah, J. Kohtz. Genes & Development, 2006

729 citations recorded by the source corpus.

The identification of ultraconserved noncoding sequences in vertebrates has been associated with developmental regulators and DNA-binding proteins. One of the first of these was identified in the intergenic region between the Dlx-5 and Dlx-6 genes, members of the Dlx/dll homeodomain-containing protein family. In previous experiments, we showed that Sonic hedgehog treatment of forebrain neural explants results in the activation of Dlx-2 and the novel noncoding RNA (ncRNA), Evf-1. In this report, we show that the Dlx-5/6 ultraconserved region is transcribed to generate an alternatively spliced form of Evf-1, the ncRNA Evf-2. Evf-2 specifically cooperates with Dlx-2 to increase the transcriptional activity of the Dlx-5/6 enhancer in a target and homeodomain-specific manner. A stable complex containing the Evf-2 ncRNA and the Dlx-2 protein forms in vivo, suggesting that the Evf-2 ncRNA activates transcriptional activity by directly influencing Dlx-2 activity. These experiments identify a novel mechanism whereby transcription is controlled by the cooperative actions of an ncRNA and a homeodomain protein. The possibility that a subset of vertebrate ultraconserved regions may function at both the DNA and RNA level to control key developmental regulators may explain why ultraconserved sequences exhibit 90% or more conservation even after 450 million years of vertebrate evolution.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/6e937bee1496befa3bf715e16bbd8e25db873779

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Citations in the corpus

Mechanisms and Functions of Long Non-Coding RNAs at Multiple Regulatory Levels (2019, background): “For example, the mouse lncRNA Evf2 is transcribed from an ultraconserved distal enhancer, which specifically binds the transcription factor DLX2, forming a transcriptional complex, and binds an enhancer, thereby inducing expression of the adjacent protein-coding gene DLX5/6 [46].”
Long non-coding RNAs with enhancer-like function in human (2010, background): “8 kb Evf-2 ncRNA was shown to form a complex with the homeodomain-containing protein Dlx2 and lead to transcriptional enhancement (Feng et al., 2006).”
Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation. (2008, background): “2007; Rougeulle and Heard 2002) and co-activation (Feng et al. 2006) during development.”
Non‐coding RNAs: regulators of disease (2010, background): “Instead, exhibition of the limb phenotype requires the expression of both the Dlx5 and Dlx6 genes to be disrupted, suggesting that SHMF1 results from the ablation of a shared regulatory element [195].”
No-nonsense functions for long noncoding RNAs. (2011, background): “Evf-2 has transcriptional regulatory activity mediated through the ultraconserved sequences at its 50 end, which forms a complex with the Dlx-2 transcription factor (Feng et al., 2006).”
Long non-coding RNAs: insights into functions (2009, background): “For example, in mice, the ncRNA Evf2 is transcribed from an ultraconserved distal enhancer and recruits the binding and action of the transcription factor DLX2 to this same enhancer to induce expression of adjacent protein-coding gene”
Long non-coding RNAs: a new frontier in the study of human diseases. (2013, background): “It serves as a transcriptional coactivator by forming a complex with Dlx2 and then, specifically binding to the Dlx-5/6 enhancer to increase its transcriptional activity in a target and homeodomain-specific manner [80].”
Evolution and functions of long noncoding RNAs. (2009, background): “Evf2 exons lie downstream of Dlx5 and surround Dlx6, both of which are homeodomain genes involved in neuronal differentiation and migration, and limb patterning (Feng et al., 2006) (Figure 1).”
Non-coding RNAs as regulators of embryogenesis (2011, background): “Initial in vitro studies suggested that Evf2 may function as a transcriptional co-activator of homeobox protein DLX2 at the Dlx5 – Dlx6 locu”
Genomic positional conservation identifies topological anchor point (tap)RNAs linked to developmental loci (2016, background): “…of SOX2OT and other pcRNAs associated with developmental genes, such as Dlx1as and Evf1/2 (Amaral et al., 2009; Bond et al., 2009; Dinger et al., 2008; Feng et al., 2006), although conserved promoters and lncRNA loci may exhibit both DNA-and RNA-dependent regulatory functions (Bond et al., 2009).”
Long noncoding RNAs: functional surprises from the RNA world. (2009, background): “Using reporter-based assays, it was shown that Dlx2 acts a transcriptional enhancer only when the Evf-2 ncRNA is also present.”