Altered Expression of the Long Noncoding RNA NEAT1 in Huntington’s Disease

Abstract

Huntington's disease (HD) is a devastating neurodegenerative disease caused by cytosine-adenine-guanine trinucleotide repeat expansion in the huntingtin gene. Growing evidence supports the regulatory functions of long noncoding RNAs (lncRNAs) in the disease process, but little is known about the association between lncRNAs and neuronal death in HD. Here, we evaluated the altered expression profiles of lncRNA in HD by using microarrays. Among dysregulated lncRNAs, we focused on the upregulation of nuclear paraspeckle assembly transcript 1 (NEAT1). Quantitative PCR analysis validated increased NEAT1 levels in the R6/2 mouse brain as well as the human HD postmortem brain. To determine the biological effects of NEAT1 on neuronal survival, neuro2A cells were transfected with the NEAT1 short isoform vector and were subjected to HO-induced injury. Subsequently, NEAT1-transfected cells showed increased viability under oxidative stress. Our observations support the notion that NEAT1 upregulation in HD contributes to the neuroprotective mechanism against neuronal injury rather than the pathological process underlying neurodegeneration in HD.

Genetic Models Reveal cis and trans Immune-Regulatory Activities for lincRNA-Cox2

“…One such example is NEAT1, which is critical for synapse formation in the brain (Sunwooet al, 2017), whereas, in adipose tissue, NEAT1 is necessary for the differentiation of white adipocytes (Cooper et al, 2014). lincRNA-Cox2 KO and mutant mice were used to globally study the cis and trans role of lincRNA-Cox2 in vivo by performing RNA-seq on lungs and spleens from LPS-challenged WT, KO, and mutant mice.…”

Functional dissection of NEAT1 using genome editing reveals substantial localization of the NEAT1_1 isoform outside paraspeckles

“…Unsurprisingly, there is also a strong link between high NEAT1 expression and more aggressive forms of cancer (Chakravarty et al 2014;Chai et al 2016;Chen et al 2016;Fu et al 2016;Ma et al 2016;Sun et al 2016;Wang et al 2016). In neurological systems, up-regulated expression of NEAT1 has also been observed in the early phase of amyotrophic lateral sclerosis and Huntington's disease, and more interestingly, its expression could also be acutely down-regulated in response to neuronal activity (Nishimoto et al 2013;Sunwoo et al 2016;Barry et al 2017). At the molecular level, NEAT1 is important for the formation of paraspeckles, a type of mammalian nuclear RNA-protein body found in close proximity to nuclear speckles (Fox et al 2002;Hutchinson et al 2007).…”

NEAT1 is overexpressed in Parkinson's disease substantia nigra and confers drug‐inducible neuroprotection from oxidative stress

“…Notably, NEAT1 also affects mitochondrial abundance and function (23). Nuclear paraspeckles have been identified as causally involved in immune responses (24) and cancer (25), and recent research on NEAT1 functions in the context of the CNS has revealed its involvement in Huntington’s disease (26) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)–induced neurotoxicity (27, 28). However, although the involvement of NEAT1 in PD has been suggested in animal models of neurodegeneration, they have not yet been thoroughly examined in human disease.…”