Functional and structural intricacies of biological systems emerge from the complex nature of the genome. A key aspect of genome complexity can be attributed to the process of alternative splicing of precursor mRNA (or pre-mRNA), during which introns are removed and exons are selectively spliced together. This highly regulated process generates different mature mRNA transcripts from a single gene and is widespread throughout the eukaryotic evolution. The majority of the genes expressed in the mammalian central nervous system undergo extensive alternative splicing. Some genes can generate more than a thousand isoforms resulting in diverse proteoforms that can differ in their function, binding preference, catalytic activity, and localization. Perturbation in alternative splicing has been linked to many neurological disorders. Despite its significance, we still lack a comprehensive understanding of its role in neuronal function.
Recent studies suggest that alternative splicing is a regulator of tissue identity and development. This is particularly relevant to the brain where developmental regulation and heterogenous cell population play a crucial role in shaping its function. For a long time, technological limitations in detecting and measuring alternatively spliced transcripts hindered the progress in understanding the biology of alternative splicing. Recent advances in long-read and native mRNA sequencing and robust computational tools allow us to capture and quantify in their full-length form. Public transcriptomics datasets can be utilized for the meta-analysis of alternative splicing landscapes of various experimental conditions and disease samples. In addition, protein isoform detection complements mRNA isoform levels. Given its biological significance and recent advances, the objective of this Research Topic is to assemble current knowledge, views, and challenges in the studies of alternative splicing in brain function.
This Research Topic aims to highlight recent conceptual and technological advances to address the significance of alternative splicing in fundamental neurobiology and pathology. Original research articles, reviews highlighting challenges and conceptual advances, and papers describing computational tools can be submitted under this Topic. Themes to be covered in this Topic include but are not limited to:
- Alternative splicing in neuronal disorders
- Therapeutic intervention of alternative splicing in the brain
- Alternative splicing in neurogenesis and development
- Molecular regulation of alternative splicing
- Alternative splicing in synaptic plasticity
- Neuronal activity-dependent alternative splicing
- Transcriptomic and computational methods to detect and quantify alternative splicing
- Single-cell transcriptomics of alternative splicing in the brain
- Alternative splicing in neuro-glial interaction
Functional and structural intricacies of biological systems emerge from the complex nature of the genome. A key aspect of genome complexity can be attributed to the process of alternative splicing of precursor mRNA (or pre-mRNA), during which introns are removed and exons are selectively spliced together. This highly regulated process generates different mature mRNA transcripts from a single gene and is widespread throughout the eukaryotic evolution. The majority of the genes expressed in the mammalian central nervous system undergo extensive alternative splicing. Some genes can generate more than a thousand isoforms resulting in diverse proteoforms that can differ in their function, binding preference, catalytic activity, and localization. Perturbation in alternative splicing has been linked to many neurological disorders. Despite its significance, we still lack a comprehensive understanding of its role in neuronal function.
Recent studies suggest that alternative splicing is a regulator of tissue identity and development. This is particularly relevant to the brain where developmental regulation and heterogenous cell population play a crucial role in shaping its function. For a long time, technological limitations in detecting and measuring alternatively spliced transcripts hindered the progress in understanding the biology of alternative splicing. Recent advances in long-read and native mRNA sequencing and robust computational tools allow us to capture and quantify in their full-length form. Public transcriptomics datasets can be utilized for the meta-analysis of alternative splicing landscapes of various experimental conditions and disease samples. In addition, protein isoform detection complements mRNA isoform levels. Given its biological significance and recent advances, the objective of this Research Topic is to assemble current knowledge, views, and challenges in the studies of alternative splicing in brain function.
This Research Topic aims to highlight recent conceptual and technological advances to address the significance of alternative splicing in fundamental neurobiology and pathology. Original research articles, reviews highlighting challenges and conceptual advances, and papers describing computational tools can be submitted under this Topic. Themes to be covered in this Topic include but are not limited to:
- Alternative splicing in neuronal disorders
- Therapeutic intervention of alternative splicing in the brain
- Alternative splicing in neurogenesis and development
- Molecular regulation of alternative splicing
- Alternative splicing in synaptic plasticity
- Neuronal activity-dependent alternative splicing
- Transcriptomic and computational methods to detect and quantify alternative splicing
- Single-cell transcriptomics of alternative splicing in the brain
- Alternative splicing in neuro-glial interaction