Figure 3.

Examples of localized action of lncRNAs in neurons

(A) NEAT1 upregulation may be protective in TDP-43 proteinopathies by mediating nuclear sequestration of TDP-43 in paraspeckles. (B) The lncRNA Adeptr is targeted to dendrites by the motor protein Kif2A upon neuronal activity, where it mediates a cAMP signaling-induced increase in spine density, supporting synaptic activity. Mechanistically, Adeptr acts as a scaffolding agent of at least two regulators of actin polymerization in neuronal dendrites: AnkyrinB and Spectrin. (C) In the wild-type (WT) mouse neocortex, binding of BC1 lncRNA to the FMRP-CYFIP1 complex and to eIF4A/B at the synapse leads to repression of PSD-95 translation, preventing its exaggerated local synthesis. By contrast, in Alzheimer’s mouse models, BC1/BC200-FMRP positively regulates APP mRNA translation. (D) In the hippocampus, binding of the β subunit of the CaMKII complex to the lncRNA Carip enhances phosphorylation of the AMPA receptor and increases conductance of the post-synaptic AMPAR channel, contributing to long-term potentiation and enhancing learning and memory.