# Polyadenylation landscape of in vivo long-term potentiation in the rat brain

## TL;DR

This study explores how mRNA ends change during synaptic plasticity in rat brains, revealing new insights into gene regulation in neurons.

## Contribution

The study provides a detailed analysis of polyadenylation dynamics during in vivo long-term potentiation using nanopore sequencing.

## Key findings

- Dynamic shifts in polyadenylation site preference and poly(A) tail lengthening occur in transcriptionally induced mRNAs after LTP induction.
- Chemical stimulation in synaptoneurosomes leads to shortening of poly(A) tails on preexisting mRNAs.
- A group of neuronal transcripts was identified with poly(A) tails rich in nonadenosine residues derived from adenosine-rich 3′UTRs.

## Abstract

Local protein synthesis in neurons is vital for synaptic maintenance and plasticity, yet the regulatory mechanisms, particularly cytoplasmic polyadenylation, are not fully understood. This study used nanopore sequencing to examine transcriptomic responses and 3′-end dynamics in rat hippocampal long-term potentiation (LTP) in vivo and in synaptoneurosomes after in vitro stimulation. Our long-read transcriptomic data set allows for detailed analysis of mRNA 3′-ends, poly(A) tail lengths, and nucleotide composition. We observed dynamic shifts in polyadenylation site preference post-LTP induction, with significant poly(A) tail lengthening restricted to transcriptionally induced mRNAs. The poly(A) tails of these genes showed increased nonadenosine abundance. In synaptoneurosomes, chemical stimulation led to the shortening of poly(A) tails on preexisting mRNAs, indicating translation-induced deadenylation. This also includes transcripts, which were previously reported to undergo stimulation-induced cytoplasmic polyadenylation, like Camk2a. Additionally, we discovered a group of neuronal transcripts with poly(A) tails abundant in nonadenosine residues. These tails are semi-templated and derived from extremely adenosine-rich 3′UTRs. This study provides a comprehensive overview of mRNA 3′-end dynamics during LTP, offering insights into post-transcriptional regulation following synaptic activation of plasticity in neurons.