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J Neurosci. 2016 Nov 9;36(45):11418-11426.

Dysregulation of mRNA Localization and Translation in Genetic Disease.

Author information

1
Center for NeuroGenetics, University of Florida, Gainesville, Florida 32610, gbassel@emory.edu eric.t.wang@ufl.edu.
2
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139-4307.
3
Department of Biological Chemistry, University of California Los Angeles, Los Angeles, California 90095-1737.
4
National Centre for Biological Sciences-TIFR, Bangalore 560065, India.
5
Manipal University, Manipal 576104, India.
6
Department of Cell Biology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322, and.
7
Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229.
8
Department of Cell Biology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322, and gbassel@emory.edu eric.t.wang@ufl.edu.

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.

KEYWORDS:

Fragile X Mental Retardation Protein (FMRP); Fragile X Syndrome (FXS); Muscleblind-like Splicing Regulator (MBNL); Myotonic Dystrophy (DM); RNA Binding Protein Fox-1 Homolog 1 (RBFOX1); Spinal Muscular Atrophy (SMA); Survival of Motor Neuron (SMN)

PMID:
27911744
PMCID:
PMC5125209
DOI:
10.1523/JNEUROSCI.2352-16.2016
[Indexed for MEDLINE]
Free PMC Article

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