RNA sequencing of synaptic and cytoplasmic Upf1-bound transcripts supports contribution of nonsense-mediated decay to epileptogenesis

Files in This Item:
File Description SizeFormat 
Mooney_2017.pdf2.55 MBAdobe PDFDownload
Title: RNA sequencing of synaptic and cytoplasmic Upf1-bound transcripts supports contribution of nonsense-mediated decay to epileptogenesis
Authors: Mooney, Claire
Jimenez-Mateos, Eva M.
Engel, Tobias
Mooney, Catherine
et al.
Permanent link: http://hdl.handle.net/10197/10063
Date: 27-Jan-2017
Online since: 2019-04-23T08:38:44Z
Abstract: The nonsense mediated decay (NMD) pathway is a critical surveillance mechanism for identifying aberrant mRNA transcripts. It is unknown, however, whether the NMD system is affected by seizures in vivo and whether changes confer beneficial or maladaptive responses that influence long-term outcomes such the network alterations that produce spontaneous recurrent seizures. Here we explored the responses of the NMD pathway to prolonged seizures (status epilepticus) and investigated the effects of NMD inhibition on epilepsy in mice. Status epilepticus led to increased protein levels of Up-frameshift suppressor 1 homolog (Upf1) within the mouse hippocampus. Upf1 protein levels were also higher in resected hippocampus from patients with intractable temporal lobe epilepsy. Immunoprecipitation of Upf1-bound RNA from the cytoplasmic and synaptosomal compartments followed by RNA sequencing identified unique populations of NMD-associated transcripts and altered levels after status epilepticus, including known substrates such as Arc as well as novel targets including Inhba and Npas4. Finally, long-term video-EEG recordings determined that pharmacologic interference in the NMD pathway after status epilepticus reduced the later occurrence of spontaneous seizures in mice. These findings suggest compartment-specific recruitment and differential loading of transcripts by NMD pathway components may contribute to the process of epileptogenesis.
Funding Details: European Commission - Seventh Framework Programme (FP7)
Higher Education Authority
Science Foundation Ireland
Type of material: Journal Article
Publisher: Springer
Journal: Scientific Reports
Volume: 7
Issue: 41517
Copyright (published version): 2017 the Authors
Keywords: Nonsense mediated decay (NMD) pathwaymRNA transcriptsStatus epilepticusNMD inhibitionEpileptogenesis
DOI: 10.1038/srep41517
Language: en
Status of Item: Peer reviewed
Appears in Collections:Computer Science Research Collection

Show full item record

Citations 50

Last Week
Last month
checked on May 17, 2019

Google ScholarTM



This item is available under the Attribution-NonCommercial-NoDerivs 3.0 Ireland. No item may be reproduced for commercial purposes. For other possible restrictions on use please refer to the publisher's URL where this is made available, or to notes contained in the item itself. Other terms may apply.