Title |
The long non-coding RNA NEAT1 is responsive to neuronal activity and is associated with hyperexcitability states
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Published in |
Scientific Reports, January 2017
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DOI | 10.1038/srep40127 |
Pubmed ID | |
Authors |
Guy Barry, James A. Briggs, Do Won Hwang, Sam P. Nayler, Patrick R. J. Fortuna, Nicky Jonkhout, Fabien Dachet, Jesper L. V. Maag, Pieter Mestdagh, Erin M. Singh, Lotta Avesson, Dominik C. Kaczorowski, Ezgi Ozturk, Nigel C. Jones, Irina Vetter, Luis Arriola-Martinez, Jianfei Hu, Gloria R. Franco, Victoria M. Warn, Andrew Gong, Marcel E. Dinger, Frank Rigo, Leonard Lipovich, Margaret J. Morris, Terence J. O’Brien, Dong Soo Lee, Jeffrey A. Loeb, Seth Blackshaw, John S. Mattick, Ernst J. Wolvetang |
Abstract |
Despite 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 2 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Austria | 1 | 1% |
Canada | 1 | 1% |
Unknown | 97 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 19 | 19% |
Student > Bachelor | 13 | 13% |
Researcher | 12 | 12% |
Student > Master | 12 | 12% |
Student > Doctoral Student | 6 | 6% |
Other | 17 | 17% |
Unknown | 20 | 20% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 31 | 31% |
Agricultural and Biological Sciences | 18 | 18% |
Neuroscience | 15 | 15% |
Medicine and Dentistry | 5 | 5% |
Computer Science | 3 | 3% |
Other | 6 | 6% |
Unknown | 21 | 21% |