DLX6 antisense RNA 1 (DLX6-AS1) (Evf-1 (Embryonic ventral forebrain-1)) is a developmentally-regulated long non-coding RNA. In rats, it is expressed in neurons in the subventricular zone of the developing forebrain. Its expression is linked to that of the Shh (sonic hedgehog) and DLX families of genes, which are important in ventral forebrain and craniofacial development.[1] An alternatively spliced form of DLX6-AS1, DLX6-AS2, forms a stable complex with the Dlx-2 protein. This complex activates transcription of Dlx-5 and Dlx-6.[2]
| Evf-2 | |
|---|---|
 Conserved secondary structure of Evf2 (an alternatively-spliced Evf1) RNA. | |
| Identifiers | |
| Symbol | Evf-2 |
| Rfam | RF01887 |
| Other data | |
| RNA type | RNA gene |
| Domain(s) | Mammalia |
| PDB structures | PDBe |
DLX6-AS2 regulates gene expression in a region of the brain which produces GABAergic interneurons during development.[3] It is involved in the signaling pathway and works in conjunction with DLX homeodomain proteins to increase the effectiveness of the Dlx5/6 enhancer element within neural stem cells. The interneurons are found in the hippocampus of the adult brain, an area responsible for learning and memory.[4]
GABAergic interneurons have been implicated in a number of psychiatric disorders including autism,[5] schizophrenia[6] and epilepsy;[7] as DLX6-AS2 controls the development of these neurons, it has been subject to studies regarding the causation of these disorders.[4]
DLX6-AS2 is the first known long non-coding RNA to be involved in organogenesis.[8]
See also
editReferences
edit- ^ Kohtz JD, Fishell G (July 2004). "Developmental regulation of EVF-1, a novel non-coding RNA transcribed upstream of the mouse Dlx6 gene". Gene Expr. Patterns. 4 (4): 407–412. doi:10.1016/j.modgep.2004.01.007. PMID 15183307.
- ^ Feng J, Bi C, Clark BS, Mady R, Shah P, Kohtz JD (June 2006). "The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator". Genes Dev. 20 (11): 1470–1484. doi:10.1101/gad.1416106. PMC 1475760. PMID 16705037.
- ^ Sciencedaily (Sep 1, 2009). "Non-Coding RNA Called Evf2 Is Important For Gene Regulation". Retrieved 26 July 2010.
- ^ a b Bond AM, Vangompel MJ, Sametsky EA, et al. (August 2009). "Balanced gene regulation by an embryonic brain ncRNA is critical for adult hippocampal GABA circuitry". Nat. Neurosci. 12 (8): 1020–1027. doi:10.1038/nn.2371. PMC 3203213. PMID 19620975.
- ^ Dani VS, Chang Q, Maffei A, Turrigiano GG, Jaenisch R, Nelson SB (August 2005). "Reduced cortical activity due to a shift in the balance between excitation and inhibition in a mouse model of Rett syndrome". Proc. Natl. Acad. Sci. U.S.A. 102 (35): 12560–12565. Bibcode:2005PNAS..10212560D. doi:10.1073/pnas.0506071102. PMC 1194957. PMID 16116096.
- ^ Lewis DA, Hashimoto T, Volk DW (April 2005). "Cortical inhibitory neurons and schizophrenia". Nat. Rev. Neurosci. 6 (4): 312–324. doi:10.1038/nrn1648. PMID 15803162. S2CID 3335493.
- ^ Di Cristo G (July 2007). "Development of cortical GABAergic circuits and its implications for neurodevelopmental disorders". Clin. Genet. 72 (1): 1–8. doi:10.1111/j.1399-0004.2007.00822.x. PMID 17594392. S2CID 22162349.[dead link]
- ^ Shamovsky I, Nudler E (October 2006). "Gene control by large noncoding RNAs". Sci. STKE. 2006 (355): pe40. doi:10.1126/stke.3552006pe40. PMID 17018852. S2CID 41151259.
Further reading
edit- Kohtz JD, Baker DP, Corte G, Fishell G (December 1998). "Regionalization within the mammalian telencephalon is mediated by changes in responsiveness to Sonic Hedgehog". Development. 125 (24): 5079–5089. doi:10.1242/dev.125.24.5079. PMID 9811591. Retrieved 2010-07-26.
- Ingham PW, McMahon AP (December 2001). "Hedgehog signaling in animal development: paradigms and principles". Genes Dev. 15 (23): 3059–3087. doi:10.1101/gad.938601. PMID 11731473.
- Licastro D, Gennarino VA, Petrera F, Sanges R, Banfi S, Stupka E (2010). "Promiscuity of enhancer, coding and non-coding transcription functions in ultraconserved elements". BMC Genomics. 11: 151. doi:10.1186/1471-2164-11-151. PMC 2847969. PMID 20202189.
- Erdmann VA, Barciszewska MZ, Hochberg A, de Groot N, Barciszewski J (June 2001). "Regulatory RNAs". Cell. Mol. Life Sci. 58 (7): 960–977. doi:10.1007/PL00000913. PMC 11337372. PMID 11497242. S2CID 19491637.