Neuronal activity regulates alternative exon usage
- PDF / 4,105,894 Bytes
- 24 Pages / 595.276 x 790.866 pts Page_size
- 110 Downloads / 198 Views
Open Access
RESEARCH
Neuronal activity regulates alternative exon usage Johanna Denkena1,2, Andrea Zaisser3, Barbara Merz3, Bertram Klinger1,2, Dietmar Kuhl3, Nils Blüthgen1,2 and Guido Hermey3*
Abstract Neuronal activity-regulated gene transcription underlies plasticity-dependent changes in the molecular composition and structure of neurons. A large number of genes regulated by different neuronal plasticity inducing pathways have been identified, but altered gene expression levels represent only part of the complexity of the activity-regulated transcriptional program. Alternative splicing, the differential inclusion and exclusion of exonic sequence in mRNA, is an additional mechanism that is thought to define the activity-dependent transcriptome. Here, we present a genome wide microarray-based survey to identify exons with increased expression levels at 1, 4 or 8 h following neuronal activity in the murine hippocampus provoked by generalized seizures. We used two different bioinformatics approaches to identify alternative activity-induced exon usage and to predict alternative splicing, ANOSVA (ANalysis Of Splicing VAriation) which we here adjusted to accommodate data from different time points and FIRMA (Finding Isoforms using Robust Multichip Analysis). RNA sequencing, in situ hybridization and reverse transcription PCR validate selected activity-dependent splicing events of previously described and so far undescribed activity-regulated transcripts, including Homer1a, Homer1d, Ania3, Errfi1, Inhba, Dclk1, Rcan1, Cda, Tpm1 and Krt75. Taken together, our survey significantly adds to the comprehensive understanding of the complex activity-dependent neuronal transcriptomic signature. In addition, we provide data sets that will serve as rich resources for future comparative expression analyses. Keywords: Neuronal activity, Synaptic plasticity, Alternative splicing, Hippocampus, Gene expression, Transcriptome, Microarray, RNA sequencing Introduction Neurons go through activity-dependent alterations in their molecular composition and structure in order to fine-tune their synaptic strength. Such neuronal plasticity plays a vital role during a critical period in the development of the nervous system [1]. In the mature brain, neuronal plasticity contributes to sensory adaptation, learning and memory formation, as well as to a variety of pathological processes such as response to injury or *Correspondence: [email protected]‑hamburg.de 3 Institute for Molecular and Cellular Cognition, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany Full list of author information is available at the end of the article
epileptogenesis and neuropsychiatric or neurodegenerative disorders [2–5]. Posttranslational modifications of pre-existing proteins are thought to convey short-term activity-dependent synaptic changes, whereas longterm maintenance of synaptic adaptations relies on gene induction [6]. Signaling from the synapse to the nucleus induces gene expr
Data Loading...
