PT  - JOURNAL ARTICLE
AU  - Vlatkovic, Irena
AU  - Sambandan, Sivakumar
AU  - Tushev, Georgi
AU  - Wang, Mantian
AU  - Epstein, Irina
AU  - Glock, Caspar
AU  - Fuerst, Nicole
AU  - Cajigas, Iván
AU  - Schuman, Erin
TI  - Poly(A) Binding Protein Nuclear 1 regulates the polyadenylation of key synaptic plasticity genes and plays a role in homeostatic plasticity
AID  - 10.1101/121194
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 121194
4099  - http://biorxiv.org/content/early/2017/03/27/121194.short
4100  - http://biorxiv.org/content/early/2017/03/27/121194.full
AB  - Polyadenylation is a nuclear process that involves the endonucleolytic cleavage of RNA transcripts and the addition of poly(A) tails. The cleavage often takes place at different positions within the same RNA transcript, generating alternative 3’ends. Polyadenylation regulates mRNA localization, stability and translation and is likely to regulate complex processes such as synapse formation, synaptic plasticity and memory. Here we examined whether PolyA Binding Protein Nuclear 1 (Pabpn1), an RNA binding protein known to regulate alternative polyadenylation and polyA tail length in other systems, regulates neuronal mRNA function. Using immunocytochemistry we determined that Pabpn1 is present in both hippocampal slices and cultured hippocampal neurons. Applying shRNAs to knock-down Pabpn1 we discovered that Pabpn1 regulates the mRNA abundance and localization of key synaptic plasticity genes including Calcium/Calmodulin Dependent Protein Kinase II Alpha (Camk2a) and Glutamate Ionotropic Receptor AMPA Type Subunit 2 (Gria2). Furthermore, Pabpn1 knock-down prevented the homeostatic scaling of synaptic transmission elicited by bicuculline. These data demonstrate a link between Pabpn1, polyadenylation and neuronal plasticity.