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.
journal_name
Sci Advjournal_title
Science advancesauthors
Keihani S,Kluever V,Mandad S,Bansal V,Rahman R,Fritsch E,Gomes LC,Gärtner A,Kügler S,Urlaub H,Wren JD,Bonn S,Rizzoli SO,Fornasiero EFdoi
10.1126/sciadv.aay2670subject
Has Abstractpub_date
2019-12-18 00:00:00pages
eaay2670issue
12issn
2375-2548pii
aay2670journal_volume
5pub_type
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