Publication Date:
2019
Description:
〈p〉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 〈i〉neuroLNC〈/i〉, a neuron-specific nuclear lncRNA conserved from rodents to humans. 〈i〉NeuroLNC〈/i〉 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 〈i〉neuroLNC〈/i〉 in detail using chromatin isolation by RNA purification, RNA interactome analysis, and protein mass spectrometry. We found that the effects of 〈i〉neuroLNC〈/i〉 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.〈/p〉
Electronic ISSN:
2375-2548
Topics:
Natural Sciences in General