Abstract
Alternative splicing of precursor mRNA is an important mechanism that increases transcriptomic and proteomic diversity and also post-transcriptionally regulates mRNA levels. Alternative splicing occurs at high frequency in brain tissues and contributes to every step of nervous system development, including cell-fate decisions, neuronal migration, axon guidance, and synaptogenesis. Genetic manipulation and RNA sequencing have provided insights into the molecular mechanisms underlying the effects of alternative splicing in stem cell self-renewal and neuronal fate specification. Timely expression and perhaps post-translational modification of neuron-specific splicing regulators play important roles in neuronal development. Alternative splicing of many key transcription regulators or epigenetic factors reprograms the transcriptome and hence contributes to stem cell fate determination. During neuronal differentiation, alternative splicing also modulates signaling activity, centriolar dynamics, and metabolic pathways. Moreover, alternative splicing impacts cortical lamination and neuronal development and function. In this review, we focus on recent progress toward understanding the contributions of alternative splicing to neurogenesis and brain development, which has shed light on how splicing defects may cause brain disorders and diseases.
Highlights
Alternative splicing is a crucial step of post-transcriptional gene expression that substantially increases transcriptome diversity and is critical for diverse cellular processes, including cell differentiation and development as well as cell reprogramming and tissue remodeling
Alternative splicing is governed by the interplay between trans-acting splicing regulators and cis-elements of pre-mRNAs (Matera and Wang, 2014)
Alternative splicing may occur in a tissue- or developmental-specific manner or in response to cellular signals and no doubt plays critical roles in many cellular processes (Nilsen and Graveley, 2010)
Summary
Reviewed by: Hidehito Kuroyanagi, Tokyo Medical and Dental University, Japan Ihab Younis, Carnegie Mellon University in Qatar, Qatar. Alternative splicing of precursor mRNA is an important mechanism that increases transcriptomic and proteomic diversity and post-transcriptionally regulates mRNA levels. Alternative splicing occurs at high frequency in brain tissues and contributes to every step of nervous system development, including cell-fate decisions, neuronal migration, axon guidance, and synaptogenesis. Genetic manipulation and RNA sequencing have provided insights into the molecular mechanisms underlying the effects of alternative splicing in stem cell self-renewal and neuronal fate specification. Expression and perhaps post-translational modification of neuron-specific splicing regulators play important roles in neuronal development. Alternative splicing of many key transcription regulators or epigenetic factors reprograms the transcriptome and contributes to stem cell fate determination. We focus on recent progress toward understanding the contributions of alternative splicing to neurogenesis and brain development, which has shed light on how splicing defects may cause brain disorders and diseases
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