Stimulus-specific remodeling of the neuronal transcriptome through nuclear intron-retaining transcripts.

Area of Science:

• Neuroscience
• Molecular Biology
• Gene Regulation

Background:

• The nuclear envelope traditionally viewed as a barrier, now recognized for regulating gene expression.
• Mechanisms controlling nuclear mRNA retention and subsequent export remain largely unknown.
• A significant portion of mRNAs are retained in the nucleus, suggesting regulated transport.

Purpose of the Study:

• To map the subcellular localization of mRNAs in mature mouse cortical neurons.
• To investigate the fate of nuclear transcripts upon neuronal stimulation.
• To elucidate the role of intron retention in neuronal transcriptome remodeling.

Main Methods:

• Comprehensive mapping of mRNA subcellular localization in mouse cortical neurons.
• Systematic analysis of nuclear transcript fate following neuronal stimulation.
• Investigation of signaling pathway activation in response to different stimuli.

Main Results:

• Nuclear-retained transcripts are predominantly stable intron-retaining mRNAs.
• Neuronal stimulation leads to either degradation or completion of splicing and export of nuclear transcripts.
• Distinct stimuli mobilize specific intron-retaining transcripts via selective signaling pathways.

Conclusions:

• Intron retention is a key regulator of acute neuronal transcriptome remodeling.
• Cue-specific control of intron retention governs mRNA fate and protein synthesis.
• This mechanism allows for rapid, stimulus-dependent changes in neuronal function.