Mechanisms of Neuronal Alternative Splicing and Strategies for Therapeutic Interventions

Many cellular and physiological processes are coordinated by regulatory networks that produce a remarkable complexity of transcript isoforms. In the mammalian nervous system, alternative pre-mRNA splicing generates functionally distinct isoforms that play key roles in normal physiology, supporting d...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of neuroscience 2019-10, Vol.39 (42), p.8193-8199
Main Authors: Lopez Soto, Eduardo Javier, Gandal, Michael J, Gonatopoulos-Pournatzis, Thomas, Heller, Elizabeth A, Luo, Diou, Zheng, Sika
Format: Article
Language:English
Subjects:
Alternative splicing
Atrophy
Cellular communication
Chromatin
Cognition
Complexity
Developmental plasticity
Isoforms
Nervous system
Phenotypes
RNA-binding protein
Spinal muscular atrophy
Symposium and Mini-Symposium
Therapeutic applications
Transcription
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Many cellular and physiological processes are coordinated by regulatory networks that produce a remarkable complexity of transcript isoforms. In the mammalian nervous system, alternative pre-mRNA splicing generates functionally distinct isoforms that play key roles in normal physiology, supporting development, plasticity, complex behaviors, and cognition. Neuronal splicing programs controlled by RNA-binding proteins, are influenced by chromatin modifications and can exhibit neuronal subtype specificity. As highlighted in recent publications, aberrant alternative splicing is a major contributor to disease phenotypes. Therefore, understanding the underlying mechanisms of alternative splicing regulation and identifying functional splicing isoforms with critical phenotypic roles are expected to provide a comprehensive resource for therapeutic development, as illuminated by recent successful interventions of spinal muscular atrophy. Here, we discuss the latest progress in the study of the emerging complexity of alternative splicing mechanisms in neurons, and how these findings inform new therapies to correct and control splicing defects.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.1149-19.2019