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

Publication date: 14 February 2017
Source:Cell Reports, Volume 18, Issue 7
Author(s): Paul G. Donlin-Asp, Claudia Fallini, Jazmin Campos, Ching-Chieh Chou, Megan E. Merritt, Han C. Phan, Gary J. Bassell, Wilfried Rossoll
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.

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Teaser

Donlin-Asp et al. show that, in both a murine model of spinal muscular atrophy and human patient samples, the association of IMP1 protein with β-actin mRNA is impaired. These results support a role for the survival of motor neuron (SMN) protein as a molecular chaperone for mRNP assembly.


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