Neuronal activity regulates alternative exon usage

Molecular Brain

Andrea Zaisser¹  Barbara Merz¹  Dietmar Kuhl¹  Guido Hermey¹  Johanna Denkena²  Nils Blüthgen²  Bertram Klinger² 

[1] Institute for Molecular and Cellular Cognition, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251, Hamburg, Germany;Institute for Theoretical Biology and Institute of Pathology, Charité-Universitätsmedizin Berlin, 10117, Berlin, Germany;Integrative Research Institute Life Sciences, Humboldt Universität Berlin, 10115, Berlin, Germany;

关键词: Neuronal activity;    Synaptic plasticity;    Alternative splicing;    Hippocampus;    Gene expression;    Transcriptome;    Microarray;    RNA sequencing;   

DOI  :  10.1186/s13041-020-00685-3

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY