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 Rossol

Research output: Contribution to journalArticle

28 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Molecular Chaperones
Motor Neurons
Neurons
Spinal Muscular Atrophy
Proteins
Messenger RNA
Small Nuclear Ribonucleoproteins
Multiprotein Complexes
Motor Neuron Disease
Ribonucleoproteins
3' Untranslated Regions
Muscular Diseases
Cytoskeleton
Molecular interactions
Actins
Carrier Proteins
messenger ribonucleoprotein
Tissue
Imaging techniques
Defects

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Donlin-Asp, P. G., Fallini, C., Campos, J., Chou, C. C., Merritt, M. E., Phan, H. C., ... Rossol, 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

The Survival of Motor Neuron Protein Acts as a Molecular Chaperone for mRNP Assembly. / Donlin-Asp, Paul G.; Fallini, Claudia; Campos, Jazmin; Chou, Ching Chieh; Merritt, Megan E.; Phan, Han C.; Bassell, Gary J.; Rossol, Wilfried.

In: Cell Reports, Vol. 18, No. 7, 14.02.2017, p. 1660-1673.

Research output: Contribution to journalArticle

Donlin-Asp, PG, Fallini, C, Campos, J, Chou, CC, Merritt, ME, Phan, HC, Bassell, GJ & Rossol, W 2017, 'The Survival of Motor Neuron Protein Acts as a Molecular Chaperone for mRNP Assembly', Cell Reports, vol. 18, no. 7, pp. 1660-1673. https://doi.org/10.1016/j.celrep.2017.01.059
Donlin-Asp PG, Fallini C, Campos J, Chou CC, Merritt ME, Phan HC et al. The Survival of Motor Neuron Protein Acts as a Molecular Chaperone for mRNP Assembly. Cell Reports. 2017 Feb 14;18(7):1660-1673. https://doi.org/10.1016/j.celrep.2017.01.059
Donlin-Asp, Paul G. ; Fallini, Claudia ; Campos, Jazmin ; Chou, Ching Chieh ; Merritt, Megan E. ; Phan, Han C. ; Bassell, Gary J. ; Rossol, Wilfried. / The Survival of Motor Neuron Protein Acts as a Molecular Chaperone for mRNP Assembly. In: Cell Reports. 2017 ; Vol. 18, No. 7. pp. 1660-1673.
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