title: Dysregulation of mRNA Localization and Translation in Genetic Disease.
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.
authors.affiliation: Center for NeuroGenetics, University of Florida, Gainesville, Florida 32610, gbassel@emory.edu eric.t.wang@ufl.edu.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Wang
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139-4307.
authors.forename: J Matthew
authors.identifier: 0000-0001-7580-1433
authors.initials: JM
authors.lastname: Taliaferro
authors.affiliation: Department of Biological Chemistry, University of California Los Angeles, Los Angeles, California 90095-1737.
authors.forename: Ji-Ann
authors.identifier: 0000-0002-9069-2113
authors.initials: JA
authors.lastname: Lee
authors.affiliation: National Centre for Biological Sciences-TIFR, Bangalore 560065, India.|Manipal University, Manipal 576104, India.
authors.forename: Indulekha P
authors.identifier: 0000-0002-4851-5156
authors.initials: IP
authors.lastname: Sudhakaran
authors.affiliation: Department of Cell Biology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322, and.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Rossoll
authors.affiliation: Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229.
authors.forename: Christina
authors.identifier: 0000-0001-6057-2527
authors.initials: C
authors.lastname: Gross
authors.affiliation: Department of Cell Biology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322, and.
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Moss
authors.affiliation: 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.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Bassell
mesh_terms: D000818:Animals; D005600:Fragile X Syndrome / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D009422:Nervous System Diseases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D016601:RNA-Binding Proteins
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)