Restoration of the Normal Splicing Pattern of the PLP1 Gene by Means of an Antisense Oligonucleotide Directed against an Exonic Mutation

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

An exonic missense mutation, c.436C>G, in the PLP1 gene of a patient affected by the hypomyelinating leukodystrophy, Pelizaeus-Merzbacher disease, has previously been found to be responsible for the alteration of the canonical alternative splicing profile of the PLP1 gene leading to the loss of the longer PLP isoform. Here we show that the presence of the c.436C>G mutation served to introduce regulatory motifs that appear to be responsible for the perturbed splicing pattern that led to loss of the major PLP transcript. With the aim of disrupting the interaction between the PLP1 splicing regulatory motifs and their cognate splicing factors, we designed an antisense oligonucleotide-based in vitro correction protocol that successfully restored PLP transcript production in oligodendrocyte precursor cells.

Original languageEnglish
Article numbere73633
JournalPLoS One
Volume8
Issue number9
DOIs
Publication statusPublished - Sep 3 2013

Fingerprint

Antisense Oligonucleotides
oligonucleotides
Restoration
Pelizaeus-Merzbacher Disease
Genes
mutation
Mutation
missense mutation
alternative splicing
Oligodendroglia
Alternative Splicing
Missense Mutation
Protein Isoforms
genes
cells
In Vitro Techniques
RNA Splicing Factors
oligodendroglia

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

@article{ae9dbb114b34470d9543d4df183d1421,
title = "Restoration of the Normal Splicing Pattern of the PLP1 Gene by Means of an Antisense Oligonucleotide Directed against an Exonic Mutation",
abstract = "An exonic missense mutation, c.436C>G, in the PLP1 gene of a patient affected by the hypomyelinating leukodystrophy, Pelizaeus-Merzbacher disease, has previously been found to be responsible for the alteration of the canonical alternative splicing profile of the PLP1 gene leading to the loss of the longer PLP isoform. Here we show that the presence of the c.436C>G mutation served to introduce regulatory motifs that appear to be responsible for the perturbed splicing pattern that led to loss of the major PLP transcript. With the aim of disrupting the interaction between the PLP1 splicing regulatory motifs and their cognate splicing factors, we designed an antisense oligonucleotide-based in vitro correction protocol that successfully restored PLP transcript production in oligodendrocyte precursor cells.",
author = "Stefano Regis and Fabio Corsolini and Serena Grossi and Barbara Tappino and Cooper, {David N.} and Mirella Filocamo",
year = "2013",
month = "9",
day = "3",
doi = "10.1371/journal.pone.0073633",
language = "English",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

TY - JOUR

T1 - Restoration of the Normal Splicing Pattern of the PLP1 Gene by Means of an Antisense Oligonucleotide Directed against an Exonic Mutation

AU - Regis, Stefano

AU - Corsolini, Fabio

AU - Grossi, Serena

AU - Tappino, Barbara

AU - Cooper, David N.

AU - Filocamo, Mirella

PY - 2013/9/3

Y1 - 2013/9/3

N2 - An exonic missense mutation, c.436C>G, in the PLP1 gene of a patient affected by the hypomyelinating leukodystrophy, Pelizaeus-Merzbacher disease, has previously been found to be responsible for the alteration of the canonical alternative splicing profile of the PLP1 gene leading to the loss of the longer PLP isoform. Here we show that the presence of the c.436C>G mutation served to introduce regulatory motifs that appear to be responsible for the perturbed splicing pattern that led to loss of the major PLP transcript. With the aim of disrupting the interaction between the PLP1 splicing regulatory motifs and their cognate splicing factors, we designed an antisense oligonucleotide-based in vitro correction protocol that successfully restored PLP transcript production in oligodendrocyte precursor cells.

AB - An exonic missense mutation, c.436C>G, in the PLP1 gene of a patient affected by the hypomyelinating leukodystrophy, Pelizaeus-Merzbacher disease, has previously been found to be responsible for the alteration of the canonical alternative splicing profile of the PLP1 gene leading to the loss of the longer PLP isoform. Here we show that the presence of the c.436C>G mutation served to introduce regulatory motifs that appear to be responsible for the perturbed splicing pattern that led to loss of the major PLP transcript. With the aim of disrupting the interaction between the PLP1 splicing regulatory motifs and their cognate splicing factors, we designed an antisense oligonucleotide-based in vitro correction protocol that successfully restored PLP transcript production in oligodendrocyte precursor cells.

UR - http://www.scopus.com/inward/record.url?scp=84883423930&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883423930&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0073633

DO - 10.1371/journal.pone.0073633

M3 - Article

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 9

M1 - e73633

ER -