The polyadenylation landscape afterin vivolong-term potentiation in the rat brain

Abstract

AbstractLocal protein synthesis in neurons is vital for synaptic plasticity, yet the regulatory mechanisms, particularly cytoplasmic polyadenylation, are not fully understood. This study employed nanopore sequencing to examine transcriptomic responses in rat hippocampi duringin vivolong-term potentiation (LTP) and in synaptoneurosomes afterin vitrostimulation. Our long-read transcriptomic dataset allows for detailed analysis of mRNA 3′-ends, poly(A) tail lengths, and composition. We observed dynamic shifts in polyadenylation site preference post-LTP induction, with significant poly(A) tail lengthening restricted to transcriptionally induced mRNAs. Poly(A) tails of these genes showed increased non-adenosine abundance. In synaptoneurosomes, chemical stimulation led to shortening of poly(A) tails on preexisting mRNAs, indicating translation-induced deadenylation. Additionally, we discovered a group of neuronal transcripts with poly(A) tails abundant in non-adenosine 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 in neuronal activation.