DLX6-AS1

{{Short description|Non-coding RNA}}

{{Infobox rfam

| Name = Evf-2

| image = Evf2-ss-cons.png

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| caption = Conserved secondary structure of Evf2 (an alternatively-spliced Evf1) RNA.

| Symbol = Evf-2

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| Rfam = RF01887

| RNA_type = RNA gene

| Tax_domain = Mammalia

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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.{{cite journal |vauthors=Kohtz JD, Fishell G |title=Developmental regulation of EVF-1, a novel non-coding RNA transcribed upstream of the mouse Dlx6 gene |journal=Gene Expr. Patterns |volume=4 |issue=4 |pages=407–412 |date=July 2004 |pmid=15183307 |doi=10.1016/j.modgep.2004.01.007 }} 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.{{cite journal |vauthors=Feng J, Bi C, Clark BS, Mady R, Shah P, Kohtz JD |title=The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator |journal=Genes Dev. |volume=20 |issue=11 |pages=1470–1484 |date=June 2006 |pmid=16705037 |pmc=1475760 |doi=10.1101/gad.1416106 }}

DLX6-AS2 regulates gene expression in a region of the brain which produces GABAergic interneurons during development.{{cite web| url=https://www.sciencedaily.com/releases/2009/08/090821163525.htm|title=Non-Coding RNA Called Evf2 Is Important For Gene Regulation|date=Sep 1, 2009|author=Sciencedaily|access-date=26 July 2010}} 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.{{cite journal |vauthors=Bond AM, Vangompel MJ, Sametsky EA |title=Balanced gene regulation by an embryonic brain ncRNA is critical for adult hippocampal GABA circuitry |journal=Nat. Neurosci. |volume=12 |issue=8 |pages=1020–1027 |date=August 2009 |pmid=19620975 |doi=10.1038/nn.2371 |pmc=3203213|display-authors=etal}}

GABAergic interneurons have been implicated in a number of psychiatric disorders including autism,{{cite journal |vauthors=Dani VS, Chang Q, Maffei A, Turrigiano GG, Jaenisch R, Nelson SB |title=Reduced cortical activity due to a shift in the balance between excitation and inhibition in a mouse model of Rett syndrome |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=102 |issue=35 |pages=12560–12565 |date=August 2005 |pmid=16116096 |pmc=1194957 |doi=10.1073/pnas.0506071102 |bibcode=2005PNAS..10212560D |doi-access=free }} schizophrenia{{cite journal |vauthors=Lewis DA, Hashimoto T, Volk DW |title=Cortical inhibitory neurons and schizophrenia |journal=Nat. Rev. Neurosci. |volume=6 |issue=4 |pages=312–324 |date=April 2005 |pmid=15803162 |doi=10.1038/nrn1648 |s2cid=3335493 }} and epilepsy;{{cite journal |author=Di Cristo G |title=Development of cortical GABAergic circuits and its implications for neurodevelopmental disorders |journal=Clin. Genet. |volume=72 |issue=1 |pages=1–8 |date=July 2007 |pmid=17594392 |doi=10.1111/j.1399-0004.2007.00822.x |s2cid=22162349 }}{{dead link|date=February 2019|bot=medic}}{{cbignore|bot=medic}} as DLX6-AS2 controls the development of these neurons, it has been subject to studies regarding the causation of these disorders.

DLX6-AS2 is the first known long non-coding RNA to be involved in organogenesis.{{cite journal |vauthors=Shamovsky I, Nudler E |title=Gene control by large noncoding RNAs |journal=Sci. STKE |volume=2006 |issue=355 |pages=pe40 |date=October 2006 |pmid=17018852 |doi=10.1126/stke.3552006pe40 |s2cid=41151259 }}