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

## TL;DR

This study shows that a specific microRNA helps form long-term memory by controlling a long non-coding RNA in a mollusc.

## Contribution

The study identifies a novel miRNA-lncRNA interaction pathway involved in one-trial learning and long-term memory formation.

## Key findings

- Lym-miR-1175 expression changes are linked to long-term memory formation in Lymnaea.
- Lym-miR-1175 negatively regulates the lncRNA Lym-NOS1AS.
- Lym-miR-1175 is essential for single-trial induced long-term memory.

## Abstract

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.

The online version contains supplementary material available at 10.1038/s41598-025-22550-w.