RT Journal Article
SR Electronic
T1 Poly(A) Binding Protein Nuclear 1 regulates the polyadenylation of key synaptic plasticity genes and plays a role in homeostatic plasticity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 121194
DO 10.1101/121194
A1 Irena Vlatkovic
A1 Sivakumar Sambandan
A1 Georgi Tushev
A1 Mantian Wang
A1 Irina Epstein
A1 Caspar Glock
A1 Nicole Fuerst
A1 Iván Cajigas
A1 Erin Schuman
YR 2017
UL http://biorxiv.org/content/early/2017/03/27/121194.abstract
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.