The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43
| Autor: | Verena Kluever, Stefan Bonn, Vikas Bansal, Henning Urlaub, J. D. Wren, Silvio O. Rizzoli, E. Fritsch, Eugenio F. Fornasiero, Annette Gärtner, L. Caldi Gomes, Sunit Mandad, Raza-Ur Rahman, Sarva Keihani, S. Kügler |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Hippocampus
Interactome chemistry.chemical_compound Mice 0302 clinical medicine Cell Movement Neurotransmitter Research Articles Neurons Neurotransmitter Agents 0303 health sciences Multidisciplinary Neurodegeneration SciAdv r-articles metabolism [Neurotransmitter Agents] Long non-coding RNA Chromatin Cell biology DNA-Binding Proteins genetics [Neurogenesis] metabolism [Neurons] RNA Long Noncoding Synaptic Vesicles RNA extraction ddc:500 metabolism [DNA-Binding Proteins] Research Article Neurogenesis Neurophysiology genetics [DNA-Binding Proteins] Mice Transgenic Transfection Synaptic vesicle metabolism [RNA Messenger] protein TDP-43 RNA neuroLNC 03 medical and health sciences Developmental Neuroscience mental disorders medicine Animals Humans RNA Messenger Rats Wistar metabolism [Synaptic Vesicles] 030304 developmental biology genetics [Cell Movement] nutritional and metabolic diseases RNA medicine.disease nervous system diseases Rats HEK293 Cells chemistry cytology [Hippocampus] metabolism [RNA Long Noncoding] 030217 neurology & neurosurgery |
| Zdroj: | Science advances 5(12), eaay2670 (2019). doi:10.1126/sciadv.aay2670 Science Advances |
| Popis: | NeuroLNC, a previously unknown long ncRNA, regulates neuronal activity by interacting with the neurodegeneration 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 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. |
| Databáze: | OpenAIRE |
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