Time dependent differential regulation of a novel long non-coding natural antisense RNA during long-term memory formation

Sergei Korneev,Jekaterina Garaliene,Gabriella Taylor,Ildikó Kemenes,György Kemenes

doi:10.1038/s41598-021-83190-4

Sergei Korneev, Jekaterina Garaliene + Show 3 more

Open Access

https://doi.org/10.1038/s41598-021-83190-4

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Journal: Scientific Reports	Publication Date: Feb 11, 2021
Citations: 3	License type: open-access

Affiliation: University of Sussex

Abstract

Long natural antisense transcripts (NATs) have been demonstrated in significant numbers in a variety of eukaryotic organisms. They are particularly prevalent in the nervous system suggesting their importance in neural functions. However, the precise physiological roles of the overwhelming majority of long NATs remain unclear. Here we report on the characterization of a novel molluscan nitric oxide synthase (NOS)-related long non-coding NAT (Lym-NOS1AS). This NAT is spliced and polyadenylated and is transcribed from the non-template strand of the Lym-NOS1 gene. We demonstrate that the Lym-NOS1AS is co-expressed with the sense Lym-NOS1 mRNA in a key neuron of memory network. Also, we report that the Lym-NOS1AS is temporally and spatially regulated by one-trial conditioning leading to long term memory (LTM) formation. Specifically, in the cerebral, but not in the buccal ganglia, the temporal pattern of changes in Lym-NOS1AS expression after training correlates with the alteration of memory lapse and non-lapse periods. Our data suggest that the Lym-NOS1AS plays a role in the consolidation of nitric oxide-dependent LTM.

Highlights

The gaseous signalling molecule nitric oxide (NO) has been implicated in the regulation of a number of important neurophysiological processes such as neurogenesis, sleep–wake cycle, appetite, hormone release, and blood pressure[1]
In our previous publications we reported on the discovery of two trans-encoded long natural antisense transcripts (NATs), which are expressed in the brain of the pond-snail, Lymnaea stagnalis, and are complementary to the nitric oxide synthase (NOS)-encoding mRNA13–16
The transcript possesses some features of a typical mRNA, such as the polyadenylation signal and a poly(A) tail, it is unlikely that it can be translated because of the presence of multiple stop codons in all the reading frames. This indicated that we had cloned a long ncRNA. Another and rather unexpected feature of this novel ncRNA was the presence of 367 nt sequence, which is complementary to the 5′ end of the Lym-NOS1 mRNA (Fig. 1a)

Summary

Introduction

The gaseous signalling molecule nitric oxide (NO) has been implicated in the regulation of a number of important neurophysiological processes such as neurogenesis, sleep–wake cycle, appetite, hormone release, and blood pressure[1]. In our previous publications we reported on the discovery of two trans-encoded long NATs (antiNOS-1 and antiNOS-2), which are expressed in the brain of the pond-snail, Lymnaea stagnalis, and are complementary to the nitric oxide synthase (NOS)-encoding mRNA13–16. Both NATs are transcribed from a NOS pseudogene and are associated with the negative regulation of the production of gaseous neurotransmitter nitric oxide (NO) by NOS. We report on the timed and targeted differential regulation of Lym-NOS1AS in the brain by reward conditioning leading to LTM formation These learninginduced changes in the expression of Lym-NOS1AS correlate well with the previously discovered alteration of memory lapse and non-lapse periods[18]

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