miRNA-1175 downregulates a long non-coding natural antisense RNA and promotes long term memory.

Single-trial induced long-term memories (LTMs) require fast removal of inhibitory memory constraints following learning. We propose that the interplay between short non-coding RNAs (sncRNAs) and long non-coding RNAs (lncRNAs) is engaged in this process, suggesting the existence of a new and unexpected pathway for LTM formation. In the mollusc Lymnaea, this pathway involves the functional interaction between a typical sncRNA, Lym-miR-1175, and a lncRNA, Lym-NOS1AS. In the current study, we validate this hypothesis and provide evidence that: (1) LTM formation in Lymnaea is associated with the timed and targeted changes in the expression of Lym-miR-1175; (2) Lym-miR-1175 is a negative regulator of the Lym-NOS1AS; (3) Lym-miR-1175 is required for single-trial induced LTM; (4) Lym-miR-1175 and Lym-NOS1AS are co-expressed in a key neuron of the Lymnaea memory network. Thus, our data indicate an important role of the interaction between a miRNA and a lncRNA in one-trial learning.