The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43
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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.
in: SCI ADV, Jahrgang 5, Nr. 12, 18.12.2019, S. eaay2670.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43
AU - Keihani, S
AU - Kluever, V
AU - Mandad, S
AU - Bansal, V
AU - Rahman, R
AU - Fritsch, E
AU - Gomes, L Caldi
AU - Gärtner, A
AU - Kügler, S
AU - Urlaub, H
AU - Wren, J D
AU - Bonn, S
AU - Rizzoli, S O
AU - Fornasiero, E F
N1 - 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).
PY - 2019/12/18
Y1 - 2019/12/18
N2 - 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.
AB - 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.
KW - Animals
KW - Cell Movement/genetics
KW - DNA-Binding Proteins/genetics
KW - HEK293 Cells
KW - Hippocampus/cytology
KW - Humans
KW - Mice
KW - Mice, Transgenic
KW - Neurogenesis/genetics
KW - Neurons/metabolism
KW - Neurotransmitter Agents/metabolism
KW - RNA, Long Noncoding/metabolism
KW - RNA, Messenger/metabolism
KW - Rats
KW - Rats, Wistar
KW - Synaptic Vesicles/metabolism
KW - Transfection
U2 - 10.1126/sciadv.aay2670
DO - 10.1126/sciadv.aay2670
M3 - SCORING: Journal article
C2 - 31897430
VL - 5
SP - eaay2670
JO - SCI ADV
JF - SCI ADV
SN - 2375-2548
IS - 12
ER -