TY - JOUR
T1 - Dysregulation of mRNA localization and translation in genetic disease
AU - Wang, Eric T.
AU - Taliaferro, J. Matthew
AU - Lee, Ji Ann
AU - Sudhakaran, Indulekha P.
AU - Rossoll, Wilfried
AU - Gross, Christina
AU - Moss, Kathryn R.
AU - Bassell, Gary J.
N1 - Publisher Copyright:
© 2016 the authors.
PY - 2016/11/9
Y1 - 2016/11/9
N2 - 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.
AB - 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.
KW - Fragile x mental retardation protein (FMRP)
KW - Fragile x syndrome (FXS)
KW - Muscleblind-like splicing regulator (MBNL)
KW - Myotonic dystrophy (DM)
KW - RNA binding protein fox-1 homolog 1 (RBFOX1)
KW - Spinal muscular atrophy (SMA)
KW - Survival of motor neuron (SMN)
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U2 - 10.1523/JNEUROSCI.2352-16.2016
DO - 10.1523/JNEUROSCI.2352-16.2016
M3 - Article
C2 - 27911744
AN - SCOPUS:84994716267
SN - 0270-6474
VL - 36
SP - 11418
EP - 11426
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 45
ER -