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The long non-coding RNA NEAT1 is responsive to neuronal activity and is associated with hyperexcitability states

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 dynami...

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Autores principales: Barry, Guy, Briggs, James A., Hwang, Do Won, Nayler, Sam P., Fortuna, Patrick R. J., Jonkhout, Nicky, Dachet, Fabien, Maag, Jesper L. V., Mestdagh, Pieter, Singh, Erin M., Avesson, Lotta, Kaczorowski, Dominik C., Ozturk, Ezgi, Jones, Nigel C., Vetter, Irina, Arriola-Martinez, Luis, Hu, Jianfei, Franco, Gloria R., Warn, Victoria M., Gong, Andrew, Dinger, Marcel E., Rigo, Frank, Lipovich, Leonard, Morris, Margaret J., O’Brien, Terence J., Lee, Dong Soo, Loeb, Jeffrey A., Blackshaw, Seth, Mattick, John S., Wolvetang, Ernst J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214838/
https://www.ncbi.nlm.nih.gov/pubmed/28054653
http://dx.doi.org/10.1038/srep40127
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author Barry, Guy
Briggs, James A.
Hwang, Do Won
Nayler, Sam P.
Fortuna, Patrick R. J.
Jonkhout, Nicky
Dachet, Fabien
Maag, Jesper L. V.
Mestdagh, Pieter
Singh, Erin M.
Avesson, Lotta
Kaczorowski, Dominik C.
Ozturk, Ezgi
Jones, Nigel C.
Vetter, Irina
Arriola-Martinez, Luis
Hu, Jianfei
Franco, Gloria R.
Warn, Victoria M.
Gong, Andrew
Dinger, Marcel E.
Rigo, Frank
Lipovich, Leonard
Morris, Margaret J.
O’Brien, Terence J.
Lee, Dong Soo
Loeb, Jeffrey A.
Blackshaw, Seth
Mattick, John S.
Wolvetang, Ernst J.
author_facet Barry, Guy
Briggs, James A.
Hwang, Do Won
Nayler, Sam P.
Fortuna, Patrick R. J.
Jonkhout, Nicky
Dachet, Fabien
Maag, Jesper L. V.
Mestdagh, Pieter
Singh, Erin M.
Avesson, Lotta
Kaczorowski, Dominik C.
Ozturk, Ezgi
Jones, Nigel C.
Vetter, Irina
Arriola-Martinez, Luis
Hu, Jianfei
Franco, Gloria R.
Warn, Victoria M.
Gong, Andrew
Dinger, Marcel E.
Rigo, Frank
Lipovich, Leonard
Morris, Margaret J.
O’Brien, Terence J.
Lee, Dong Soo
Loeb, Jeffrey A.
Blackshaw, Seth
Mattick, John S.
Wolvetang, Ernst J.
author_sort Barry, Guy
collection PubMed
description 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.
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spelling pubmed-52148382017-01-09 The long non-coding RNA NEAT1 is responsive to neuronal activity and is associated with hyperexcitability states Barry, Guy Briggs, James A. Hwang, Do Won Nayler, Sam P. Fortuna, Patrick R. J. Jonkhout, Nicky Dachet, Fabien Maag, Jesper L. V. Mestdagh, Pieter Singh, Erin M. Avesson, Lotta Kaczorowski, Dominik C. Ozturk, Ezgi Jones, Nigel C. Vetter, Irina Arriola-Martinez, Luis Hu, Jianfei Franco, Gloria R. Warn, Victoria M. Gong, Andrew Dinger, Marcel E. Rigo, Frank Lipovich, Leonard Morris, Margaret J. O’Brien, Terence J. Lee, Dong Soo Loeb, Jeffrey A. Blackshaw, Seth Mattick, John S. Wolvetang, Ernst J. Sci Rep Article 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. Nature Publishing Group 2017-01-05 /pmc/articles/PMC5214838/ /pubmed/28054653 http://dx.doi.org/10.1038/srep40127 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Barry, Guy
Briggs, James A.
Hwang, Do Won
Nayler, Sam P.
Fortuna, Patrick R. J.
Jonkhout, Nicky
Dachet, Fabien
Maag, Jesper L. V.
Mestdagh, Pieter
Singh, Erin M.
Avesson, Lotta
Kaczorowski, Dominik C.
Ozturk, Ezgi
Jones, Nigel C.
Vetter, Irina
Arriola-Martinez, Luis
Hu, Jianfei
Franco, Gloria R.
Warn, Victoria M.
Gong, Andrew
Dinger, Marcel E.
Rigo, Frank
Lipovich, Leonard
Morris, Margaret J.
O’Brien, Terence J.
Lee, Dong Soo
Loeb, Jeffrey A.
Blackshaw, Seth
Mattick, John S.
Wolvetang, Ernst J.
The long non-coding RNA NEAT1 is responsive to neuronal activity and is associated with hyperexcitability states
title The long non-coding RNA NEAT1 is responsive to neuronal activity and is associated with hyperexcitability states
title_full The long non-coding RNA NEAT1 is responsive to neuronal activity and is associated with hyperexcitability states
title_fullStr The long non-coding RNA NEAT1 is responsive to neuronal activity and is associated with hyperexcitability states
title_full_unstemmed The long non-coding RNA NEAT1 is responsive to neuronal activity and is associated with hyperexcitability states
title_short The long non-coding RNA NEAT1 is responsive to neuronal activity and is associated with hyperexcitability states
title_sort long non-coding rna neat1 is responsive to neuronal activity and is associated with hyperexcitability states
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214838/
https://www.ncbi.nlm.nih.gov/pubmed/28054653
http://dx.doi.org/10.1038/srep40127
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