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  The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43

Keihani, S., Klüver, V., Mandad, S., Bansal, V., Rahman, R., Fritsch, E., et al. (2019). The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43. Science Advances, 5(12): eaay2670. doi:10.1126/sciadv.aay2670.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-797C-9 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-7980-2
Genre: Journal Article

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Keihani, S., Author
Klüver, V1, Author              
Mandad, S.1, Author              
Bansal, V., Author
Rahman, R., Author
Fritsch, E., Author
Gomes, L. C., Author
Gärtner, A., Author
Kügler, S., Author
Urlaub, H.1, Author              
Wren, J. D., Author
Bonn, S., Author
Rizzoli, S. O., Author
Fornasiero, E. F., Author
Affiliations:
1Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society, ou_578613              

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 Abstract: 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.

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Language(s): eng - English
 Dates: 2019-12-042019-12-18
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1126/sciadv.aay2670
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Title: Science Advances
Source Genre: Journal
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Pages: 17 Volume / Issue: 5 (12) Sequence Number: eaay2670 Start / End Page: - Identifier: -