Journal
MOLECULAR AND CELLULAR NEUROSCIENCE
Volume 87, Issue -, Pages 35-45Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2017.10.006
Keywords
Alternative splicing; Microexons; Chromatin; Transcription factors; Neuronal isoforms; Neurodevelopmental disorders
Categories
Funding
- University of Michigan Career Training in Reproductive Biology [T32 HD079342]
- NIH [F31 NS103377, R01 NS089896]
- University of Michigan Medical School
- NIH
- Farrehi Research Fund
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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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