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dc.contributor.authorBarry, G
dc.contributor.authorBriggs, JA
dc.contributor.authorHwang, DW
dc.contributor.authorNayler, SP
dc.contributor.authorFortuna, PRJ
dc.contributor.authorJonkhout, N
dc.contributor.authorDachet, F
dc.contributor.authorMaag, JLV
dc.contributor.authorMestdagh, P
dc.contributor.authorSingh, EM
dc.contributor.authorAvesson, L
dc.contributor.authorKaczorowski, DC
dc.contributor.authorOzturk, E
dc.contributor.authorJones, NC
dc.contributor.authorVetter, I
dc.contributor.authorArriola-Martinez, L
dc.contributor.authorHu, J
dc.contributor.authorFranco, GR
dc.contributor.authorWarn, VM
dc.contributor.authorGong, A
dc.contributor.authorDinger, ME
dc.contributor.authorRigo, F
dc.contributor.authorLipovich, L
dc.contributor.authorMorris, MJ
dc.contributor.authorO'Brien, TJ
dc.contributor.authorLee, DS
dc.contributor.authorLoeb, JA
dc.contributor.authorBlackshaw, S
dc.contributor.authorMattick, JS
dc.contributor.authorWolvetang, EJ
dc.date.accessioned2020-12-22T03:11:04Z
dc.date.available2020-12-22T03:11:04Z
dc.date.issued2017-01-05
dc.identifierpii: srep40127
dc.identifier.citationBarry, G., Briggs, J. A., Hwang, D. W., Nayler, S. P., Fortuna, P. R. J., Jonkhout, N., Dachet, F., Maag, J. L. V., Mestdagh, P., Singh, E. M., Avesson, L., Kaczorowski, D. C., Ozturk, E., Jones, N. C., Vetter, I., Arriola-Martinez, L., Hu, J., Franco, G. R., Warn, V. M. ,... Wolvetang, E. J. (2017). The long non-coding RNA NEAT1 is responsive to neuronal activity and is associated with hyperexcitability states. SCIENTIFIC REPORTS, 7 (1), https://doi.org/10.1038/srep40127.
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/11343/257797
dc.description.abstractDespite their abundance, the molecular functions of long non-coding RNAs in mammalian nervous systems remain poorly understood. Here we show that the long non-coding RNA, NEAT1, directly modulates neuronal excitability and is associated with pathological seizure states. Specifically, NEAT1 is dynamically regulated by neuronal activity in vitro and in vivo, binds epilepsy-associated potassium channel-interacting proteins including KCNAB2 and KCNIP1, and induces a neuronal hyper-potentiation phenotype in iPSC-derived human cortical neurons following antisense oligonucleotide knockdown. Next generation sequencing reveals a strong association of NEAT1 with increased ion channel gene expression upon activation of iPSC-derived neurons following NEAT1 knockdown. Furthermore, we show that while NEAT1 is acutely down-regulated in response to neuronal activity, repeated stimulation results in NEAT1 becoming chronically unresponsive in independent in vivo rat model systems relevant to temporal lobe epilepsy. We extended previous studies showing increased NEAT1 expression in resected cortical tissue from high spiking regions of patients suffering from intractable seizures. Our results indicate a role for NEAT1 in modulating human neuronal activity and suggest a novel mechanistic link between an activity-dependent long non-coding RNA and epilepsy.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleThe long non-coding RNA NEAT1 is responsive to neuronal activity and is associated with hyperexcitability states
dc.typeJournal Article
dc.identifier.doi10.1038/srep40127
melbourne.affiliation.departmentMedicine (RMH)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleScientific Reports
melbourne.source.volume7
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1174594
melbourne.contributor.authorO'Brien, Terence
melbourne.contributor.authorOzturk, Ezgi
melbourne.contributor.authorJones, Nigel
dc.identifier.eissn2045-2322
melbourne.accessrightsOpen Access


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