mRNA expression, splicing and editing in the embryonic and adult mouse cerebral cortex

Abstract

The complexity of the adult brain is a result of both developmental processes and experience-dependent circuit formation. One way to look at the differences between embryonic and adult brain is to examine gene expression. Previous studies have used microarrays to address this in a global manner. However, the transcriptome is more complex than gene expression levels alone, as alternative splicing and RNA editing generate a diverse set of mature transcripts. Here, we developed a high-resolution transcriptome dataset of mouse cerebral cortex at embryonic and adult stages using RNA sequencing (RNA-Seq). We found many differences in gene expression, splicing and RNA editing between embryonic and adult cerebral cortex. Each dataset was validated technically and biologically, and in each case we found our RNA-Seq observations to have predictive validity. We propose this dataset and analysis to be a helpful resource for understanding gene expression in the embryonic and adult cerebral cortex.

ADAR2 affects mRNA coding sequence edits with only modest effects on gene expression or splicingin vivo

“…these sites have been previously identified in our work 20 or by Wahlstedt et al, 8 suggesting they are both technically and biologically robust. The number of edited sites is lower than some previous estimates, likely because we used very stringent filtering to allow for more robust comparisons between groups.…”

“…20 Instead, we propose that at least in mouse frontal cortex ADAR2 has a predominant role in control of protein diversity, supported by the observation that there is an excess of changes in editing sites that are in coding regions. We speculate that ADAR2 may have evolved a specific function that is distinct from the effect of ADAR1 on editing RNA species in response to infection.…”

From sauropsids to mammals and back: New approaches to comparative cortical development

“…Developmental compartments have been shown to express specific gene‐signatures (Ayoub et al, 2011; Fietz et al, 2012) differing across ontogeny. Thus, a cohort of active transcripts during development and in adult cortical compartments can be differentiated at the level of gene expression, splicing, and RNA editing (Dillman et al, 2013). Differential set of transcripts are also expressed across phylogeny: thus, neocortical common and species‐specific gene signatures can be found for closely related species like monkey and human, and across more distant species like mouse and human (Ayoub et al, 2011; Hou et al, 2012).…”

Analysis and design of RNA sequencing experiments for identifying RNA editing and other single-nucleotide variants

“…Recently, high-throughput RNA-sequencing (RNA-Seq) data were analyzed in multiple studies to identify RNA-DNA mismatches in mammalian mRNAs (Li et al 2011;Bahn et al 2012;Chen et al 2012;Danecek et al 2012;Gu et al 2012;Park et al 2012;Peng et al 2012;Ramaswami et al 2012Ramaswami et al , 2013Dillman et al 2013;Lagarrigue et al 2013). One of the first studies reported a striking list of all 12 types of RNA-DNA differences (RDDs) in human cells (Li et al 2011), while others presented opposing results (Schrider et al 2011;Bahn et al 2012;Danecek et al 2012;Gu et al 2012;Park et al 2012;Peng et al 2012;Ramaswami et al 2012).…”