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Mol Cell Neurosci. 2018 Mar;87:35-45. doi: 10.1016/j.mcn.2017.10.006. Epub 2017 Dec 15.

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

Author information

1
Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
2
The University of Michigan College of Literature, Science, and the Arts, Ann Arbor, MI, USA.
3
Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA. Electronic address: siwase@umich.edu.

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.

KEYWORDS:

Alternative splicing; Chromatin; Microexons; Neurodevelopmental disorders; Neuronal isoforms; Transcription factors

PMID:
29254826
PMCID:
PMC5828955
DOI:
10.1016/j.mcn.2017.10.006
[Indexed for MEDLINE]
Free PMC Article

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