Exon expression profiling reveals stimulus-mediated exon use in neural cells

Area of Science:

• Neuroscience
• Molecular Biology
• Genomics

Background:

• Neuronal cells regulate gene expression through changes in intracellular calcium ([Ca2+]i).
• Calcium influences both mRNA abundance and architecture.
• The interplay between calcium-induced transcription and transcript variation was not previously studied genome-wide.

Purpose of the Study:

• To investigate the genome-wide interplay between calcium-induced transcription and transcript variation.
• To analyze how intracellular calcium ([Ca2+]i) affects gene expression at both transcript and exon levels.

Main Methods:

• Utilized exon-centric microarrays to differentiate transcript-level and exon-level gene regulation.
• Performed global assessments of calcium-modulated transcripts and exons.

Main Results:

• Identified distinct functional gene categories modulated by [Ca2+]i.
• Found enrichment for calcium ion binding, calmodulin binding, plasma membrane, and metabolic proteins in transcripts with calcium-modulated exons.
• Observed regulated exon use in potassium channels, neuroendocrine secretory proteins, and metabolic enzymes, leading to distinct transcript variants.

Conclusions:

• Extracellular stimuli connect to specific exon behavior.
• Changes in transcript and exon abundance reflect a coordinated gene expression response to elevated [Ca2+]i.
• Developed technology to resolve stimulus-induced gene expression at transcript and exon levels.