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

doi:10.1016/j.celrep.2017.01.059

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

Neuroscience

Research output: Contribution to journal › Article › peer-review

38 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 language	English (US)
Pages (from-to)	1660-1673
Number of pages	14
Journal	Cell reports
Volume	18
Issue number	7
DOIs	https://doi.org/10.1016/j.celrep.2017.01.059
State	Published - 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)

Access to Document

10.1016/j.celrep.2017.01.059

Cite this

@article{e89f8fdca85246a9801af8fdc1d85f5f,

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.",

keywords = "IMP1, SMA, SMN, beta actin mRNA, mRNA localization, mRNP, spinal muscular atrophy",

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

note = "Funding Information: The authors thank Lian Li and Shirley Huang for excellent technical support. This work was supported by the Muscular Dystrophy Association (MDA) and Weissman Family Foundation (G.J.B.), NIH grant NS091749 to W.R., and National Research Service Award (NRSA) training award F31NS084730-01 and ARCS Fellowship Roche Foundation award to P.G.D.-A. This research project was supported in part by the Emory University Integrated Cellular Imaging Microscopy Core of the Emory Neuroscience NINDS Core Facilities grant P30NS055077. This study used samples from the NINDS Cell Line Repository (https://catalog.coriell.org/1/NINDS), as well as clinical data. NINDS and NIGMS Repository sample numbers corresponding to the samples used are ND29178, ND29179, GM09677, and GM00232. Publisher Copyright: {\textcopyright} 2017 The Authors",

year = "2017",

month = feb,

day = "14",

doi = "10.1016/j.celrep.2017.01.059",

language = "English (US)",

volume = "18",

pages = "1660--1673",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "7",

}

TY - JOUR

T1 - The Survival of Motor Neuron Protein Acts as a Molecular Chaperone for mRNP Assembly

AU - Donlin-Asp, Paul G.

AU - Fallini, Claudia

AU - Campos, Jazmin

AU - Chou, Ching Chieh

AU - Merritt, Megan E.

AU - Phan, Han C.

AU - Bassell, Gary J.

AU - Rossoll, Wilfried

N1 - Funding Information: The authors thank Lian Li and Shirley Huang for excellent technical support. This work was supported by the Muscular Dystrophy Association (MDA) and Weissman Family Foundation (G.J.B.), NIH grant NS091749 to W.R., and National Research Service Award (NRSA) training award F31NS084730-01 and ARCS Fellowship Roche Foundation award to P.G.D.-A. This research project was supported in part by the Emory University Integrated Cellular Imaging Microscopy Core of the Emory Neuroscience NINDS Core Facilities grant P30NS055077. This study used samples from the NINDS Cell Line Repository (https://catalog.coriell.org/1/NINDS), as well as clinical data. NINDS and NIGMS Repository sample numbers corresponding to the samples used are ND29178, ND29179, GM09677, and GM00232. Publisher Copyright: © 2017 The Authors

PY - 2017/2/14

Y1 - 2017/2/14

N2 - 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.

AB - 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.

KW - IMP1

KW - SMA

KW - SMN

KW - beta actin mRNA

KW - mRNA localization

KW - mRNP

KW - spinal muscular atrophy

UR - http://www.scopus.com/inward/record.url?scp=85013178200&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85013178200&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2017.01.059

DO - 10.1016/j.celrep.2017.01.059

M3 - Article

C2 - 28199839

AN - SCOPUS:85013178200

SN - 2211-1247

VL - 18

SP - 1660

EP - 1673

JO - Cell Reports

JF - Cell Reports

IS - 7

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this