TitleDysregulation of mRNA Localization and Translation in Genetic Disease.
Publication TypeJournal Article
Year of Publication2016
AuthorsWang ET, J Taliaferro M, Lee J-A, Sudhakaran IP, Rossoll W, Gross C, Moss KR, Bassell GJ
JournalJ Neurosci
Volume36
Issue45
Pagination11418-11426
Date Published2016 Nov 09
ISSN1529-2401
Abstract

RNA-binding proteins (RBPs) acting at various steps in the post-transcriptional regulation of gene expression play crucial roles in neuronal development and synaptic plasticity. Genetic mutations affecting several RBPs and associated factors lead to diverse neurological symptoms, as characterized by neurodevelopmental and neuropsychiatric disorders, neuromuscular and neurodegenerative diseases, and can often be multisystemic diseases. We will highlight the physiological roles of a few specific proteins in molecular mechanisms of cytoplasmic mRNA regulation, and how these processes are dysregulated in genetic disease. Recent advances in computational biology and genomewide analysis, integrated with diverse experimental approaches and model systems, have provided new insights into conserved mechanisms and the shared pathobiology of mRNA dysregulation in disease. Progress has been made to understand the pathobiology of disease mechanisms for myotonic dystrophy, spinal muscular atrophy, and fragile X syndrome, with broader implications for other RBP-associated genetic neurological diseases. This gained knowledge of underlying basic mechanisms has paved the way to the development of therapeutic strategies targeting disease mechanisms.

DOI10.1523/JNEUROSCI.2352-16.2016
Alternate JournalJ. Neurosci.
PubMed ID27911744
PubMed Central IDPMC5125209