Dec 20, 2017

Neuron-specific alternative splicing of transcriptional machineries: Implications for neurodevelopmental disorders

Molecular and Cellular Neurosciences
Robert S PorterShigeki Iwase

Abstract

The brain has long been known to display the most complex pattern of alternative splicing, thereby producing diverse protein isoforms compared to other tissues. Recent evidence indicates that many alternative exons are neuron-specific, evolutionarily conserved, and found in regulators of transcription including DNA-binding protein and histone modifying enzymes. This raises a possibility that neurons adopt unique mechanisms of transcription. Given that transcriptional machineries are frequently mutated in neurodevelopmental disorders with cognitive dysfunction, it is important to understand how neuron-specific alternative splicing contributes to proper transcriptional regulation in the brain. In this review, we summarize current knowledge regarding how neuron-specific splicing events alter the function of transcriptional regulators and shape unique gene expression patterns in the brain and the implications of neuronal splicing to the pathophysiology of neurodevelopmental disorders.

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Mentioned in this Paper

Nested Transcripts
Transcriptional Regulation
Patterns
Histone antigen
Exons
Enzymes, antithrombotic
Transcription, Genetic
Neurons
Brain
Transcription Process

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