title: The Survival of Motor Neuron Protein Acts as a Molecular Chaperone for mRNP Assembly.
abstract: Spinal muscular atrophy (SMA) is a motor neuron disease caused by reduced levels of the survival of motor neuron (SMN) protein. SMN is part of a multiprotein complex that facilitates the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs). SMN has also been found to associate with mRNA-binding proteins, but the nature of this association was unknown. Here, we have employed a combination of biochemical and advanced imaging methods to demonstrate that SMN promotes the molecular interaction between IMP1 protein and the 3' UTR zipcode region of β-actin mRNA, leading to assembly of messenger ribonucleoprotein (mRNP) complexes that associate with the cytoskeleton to facilitate trafficking. We have identified defects in mRNP assembly in cells and tissues from SMA disease models and patients that depend on the SMN Tudor domain and explain the observed deficiency in mRNA localization and local translation, providing insight into SMA pathogenesis as a ribonucleoprotein (RNP)-assembly disorder.
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Donlin-Asp
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fallini
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Jazmin
authors.initials: J
authors.lastname: Campos
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Ching-Chieh
authors.initials: CC
authors.lastname: Chou
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA; Laboratory of Translational Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Merritt
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Han C
authors.initials: HC
authors.lastname: Phan
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA; Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA; Laboratory of Translational Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: gbassel@emory.edu.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Bassell
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA; Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA; Laboratory of Translational Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: wrossol@emory.edu.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Rossoll
mesh_terms: D020413:3' Untranslated Regions / Q000502:physiology; D000199:Actins / Q000378:metabolism; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism*; D009134:Muscular Atrophy, Spinal / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism*; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism; D055532:SMN Complex Proteins / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D000199:Actins; C406144:IGF2BP1 protein, human; D018832:Molecular Chaperones; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D055532:SMN Complex Proteins; C026452:messenger ribonucleoprotein
keywords: IMP1; SMA; SMN; beta actin mRNA; mRNA localization; mRNP; spinal muscular atrophy