Format

Send to

Choose Destination
Cell Rep. 2017 Feb 14;18(7):1660-1673. doi: 10.1016/j.celrep.2017.01.059.

The Survival of Motor Neuron Protein Acts as a Molecular Chaperone for mRNP Assembly.

Author information

1
Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
2
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.
3
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA.
4
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.
5
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.

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.

KEYWORDS:

IMP1; SMA; SMN; beta actin mRNA; mRNA localization; mRNP; spinal muscular atrophy

PMID:
28199839
PMCID:
PMC5492976
DOI:
10.1016/j.celrep.2017.01.059
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center