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

Paul G. Donlin-Asp, Claudia Fallini, Jazmin Campos, Ching Chieh Chou, Megan E. Merritt, Han C. Phan, Gary J. Bassell, Wilfried Rossoll

Research output: Contribution to journalArticle

30 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1660-1673
Number of pages14
JournalCell reports
Volume18
Issue number7
DOIs
StatePublished - Feb 14 2017

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Donlin-Asp, P. G., Fallini, C., Campos, J., Chou, C. C., Merritt, M. E., Phan, H. C., Bassell, G. J., & Rossoll, W. (2017). The Survival of Motor Neuron Protein Acts as a Molecular Chaperone for mRNP Assembly. Cell reports, 18(7), 1660-1673. https://doi.org/10.1016/j.celrep.2017.01.059