Cargando…
The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43
The cellular and the molecular mechanisms by which long noncoding RNAs (lncRNAs) may regulate presynaptic function and neuronal activity are largely unexplored. Here, we established an integrated screening strategy to discover lncRNAs implicated in neurotransmitter and synaptic vesicle release. With...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920028/ https://www.ncbi.nlm.nih.gov/pubmed/31897430 http://dx.doi.org/10.1126/sciadv.aay2670 |
_version_ | 1783480861066264576 |
---|---|
author | Keihani, S. Kluever, V. Mandad, S. Bansal, V. Rahman, R. Fritsch, E. Gomes, L. Caldi Gärtner, A. Kügler, S. Urlaub, H. Wren, J. D. Bonn, S. Rizzoli, S. O. Fornasiero, E. F. |
author_facet | Keihani, S. Kluever, V. Mandad, S. Bansal, V. Rahman, R. Fritsch, E. Gomes, L. Caldi Gärtner, A. Kügler, S. Urlaub, H. Wren, J. D. Bonn, S. Rizzoli, S. O. Fornasiero, E. F. |
author_sort | Keihani, S. |
collection | PubMed |
description | The cellular and the molecular mechanisms by which long noncoding RNAs (lncRNAs) may regulate presynaptic function and neuronal activity are largely unexplored. Here, we established an integrated screening strategy to discover lncRNAs implicated in neurotransmitter and synaptic vesicle release. With this approach, we identified neuroLNC, a neuron-specific nuclear lncRNA conserved from rodents to humans. NeuroLNC is tuned by synaptic activity and influences several other essential aspects of neuronal development including calcium influx, neuritogenesis, and neuronal migration in vivo. We defined the molecular interactors of neuroLNC in detail using chromatin isolation by RNA purification, RNA interactome analysis, and protein mass spectrometry. We found that the effects of neuroLNC on synaptic vesicle release require interaction with the RNA-binding protein TDP-43 (TAR DNA binding protein-43) and the selective stabilization of mRNAs encoding for presynaptic proteins. These results provide the first proof of an lncRNA that orchestrates neuronal excitability by influencing presynaptic function. |
format | Online Article Text |
id | pubmed-6920028 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-69200282020-01-02 The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43 Keihani, S. Kluever, V. Mandad, S. Bansal, V. Rahman, R. Fritsch, E. Gomes, L. Caldi Gärtner, A. Kügler, S. Urlaub, H. Wren, J. D. Bonn, S. Rizzoli, S. O. Fornasiero, E. F. Sci Adv Research Articles The cellular and the molecular mechanisms by which long noncoding RNAs (lncRNAs) may regulate presynaptic function and neuronal activity are largely unexplored. Here, we established an integrated screening strategy to discover lncRNAs implicated in neurotransmitter and synaptic vesicle release. With this approach, we identified neuroLNC, a neuron-specific nuclear lncRNA conserved from rodents to humans. NeuroLNC is tuned by synaptic activity and influences several other essential aspects of neuronal development including calcium influx, neuritogenesis, and neuronal migration in vivo. We defined the molecular interactors of neuroLNC in detail using chromatin isolation by RNA purification, RNA interactome analysis, and protein mass spectrometry. We found that the effects of neuroLNC on synaptic vesicle release require interaction with the RNA-binding protein TDP-43 (TAR DNA binding protein-43) and the selective stabilization of mRNAs encoding for presynaptic proteins. These results provide the first proof of an lncRNA that orchestrates neuronal excitability by influencing presynaptic function. American Association for the Advancement of Science 2019-12-18 /pmc/articles/PMC6920028/ /pubmed/31897430 http://dx.doi.org/10.1126/sciadv.aay2670 Text en Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Keihani, S. Kluever, V. Mandad, S. Bansal, V. Rahman, R. Fritsch, E. Gomes, L. Caldi Gärtner, A. Kügler, S. Urlaub, H. Wren, J. D. Bonn, S. Rizzoli, S. O. Fornasiero, E. F. The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43 |
title | The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43 |
title_full | The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43 |
title_fullStr | The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43 |
title_full_unstemmed | The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43 |
title_short | The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43 |
title_sort | long noncoding rna neurolnc regulates presynaptic activity by interacting with the neurodegeneration-associated protein tdp-43 |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920028/ https://www.ncbi.nlm.nih.gov/pubmed/31897430 http://dx.doi.org/10.1126/sciadv.aay2670 |
work_keys_str_mv | AT keihanis thelongnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT klueverv thelongnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT mandads thelongnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT bansalv thelongnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT rahmanr thelongnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT fritsche thelongnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT gomeslcaldi thelongnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT gartnera thelongnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT kuglers thelongnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT urlaubh thelongnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT wrenjd thelongnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT bonns thelongnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT rizzoliso thelongnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT fornasieroef thelongnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT keihanis longnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT klueverv longnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT mandads longnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT bansalv longnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT rahmanr longnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT fritsche longnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT gomeslcaldi longnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT gartnera longnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT kuglers longnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT urlaubh longnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT wrenjd longnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT bonns longnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT rizzoliso longnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 AT fornasieroef longnoncodingrnaneurolncregulatespresynapticactivitybyinteractingwiththeneurodegenerationassociatedproteintdp43 |