RBFOX1 cooperates with MBNL1 to control splicing in muscle, including events altered in myotonic dystrophy type 1

Roscoe Klinck, Angélique Fourrier, Philippe Thibault, Johanne Toutant, Mathieu Durand, Elvy Lapointe, Marie Laure Caillet-Boudin, Nicolas Sergeant, Genevieve Gourdon, Giovanni Meola, Denis Furling, Jack Puymirat, Benoit Chabot

Research output: Contribution to journalArticle

Abstract

With the goal of identifying splicing alterations in myotonic dystrophy 1 (DM1) tissues that may yield insights into targets or mechanisms, we have surveyed mis-splicing events in three systems using a RT-PCR screening and validation platform. First, a transgenic mouse model expressing CUG-repeats identified splicing alterations shared with other mouse models of DM1. Second, using cell cultures from human embryonic muscle, we noted that DM1-associated splicing alterations were significantly enriched in cytoskeleton (e.g. SORBS1, TACC2, TTN, ACTN1 and DMD) and channel (e.g. KCND3 and TRPM4) genes. Third, of the splicing alterations occurring in adult DM1 tissues, one produced a dominant negative variant of the splicing regulator RBFOX1. Notably, half of the splicing events controlled by MBNL1 were co-regulated by RBFOX1, and several events in this category were mis-spliced in DM1 tissues. Our results suggest that reduced RBFOX1 activity in DM1 tissues may amplify several of the splicing alterations caused by the deficiency in MBNL1.

Original languageEnglish
Article numbere107324
JournalPLoS One
Volume9
Issue number9
DOIs
Publication statusPublished - Sep 1 2014

Fingerprint

Myotonic Dystrophy
Muscle
Tissue
Muscles
muscles
animal models
cytoskeleton
Cytoskeleton
Cell culture
Transgenic Mice
Screening
cell culture
Cell Culture Techniques
Genes
reverse transcriptase polymerase chain reaction
genetically modified organisms
screening
Polymerase Chain Reaction
tissues
genes

ASJC Scopus subject areas

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

Cite this

Klinck, R., Fourrier, A., Thibault, P., Toutant, J., Durand, M., Lapointe, E., ... Chabot, B. (2014). RBFOX1 cooperates with MBNL1 to control splicing in muscle, including events altered in myotonic dystrophy type 1. PLoS One, 9(9), [e107324]. https://doi.org/10.1371/journal.pone.0107324

RBFOX1 cooperates with MBNL1 to control splicing in muscle, including events altered in myotonic dystrophy type 1. / Klinck, Roscoe; Fourrier, Angélique; Thibault, Philippe; Toutant, Johanne; Durand, Mathieu; Lapointe, Elvy; Caillet-Boudin, Marie Laure; Sergeant, Nicolas; Gourdon, Genevieve; Meola, Giovanni; Furling, Denis; Puymirat, Jack; Chabot, Benoit.

In: PLoS One, Vol. 9, No. 9, e107324, 01.09.2014.

Research output: Contribution to journalArticle

Klinck, R, Fourrier, A, Thibault, P, Toutant, J, Durand, M, Lapointe, E, Caillet-Boudin, ML, Sergeant, N, Gourdon, G, Meola, G, Furling, D, Puymirat, J & Chabot, B 2014, 'RBFOX1 cooperates with MBNL1 to control splicing in muscle, including events altered in myotonic dystrophy type 1', PLoS One, vol. 9, no. 9, e107324. https://doi.org/10.1371/journal.pone.0107324
Klinck, Roscoe ; Fourrier, Angélique ; Thibault, Philippe ; Toutant, Johanne ; Durand, Mathieu ; Lapointe, Elvy ; Caillet-Boudin, Marie Laure ; Sergeant, Nicolas ; Gourdon, Genevieve ; Meola, Giovanni ; Furling, Denis ; Puymirat, Jack ; Chabot, Benoit. / RBFOX1 cooperates with MBNL1 to control splicing in muscle, including events altered in myotonic dystrophy type 1. In: PLoS One. 2014 ; Vol. 9, No. 9.
@article{aa613ed3de9544cba94e86b69156001f,
title = "RBFOX1 cooperates with MBNL1 to control splicing in muscle, including events altered in myotonic dystrophy type 1",
abstract = "With the goal of identifying splicing alterations in myotonic dystrophy 1 (DM1) tissues that may yield insights into targets or mechanisms, we have surveyed mis-splicing events in three systems using a RT-PCR screening and validation platform. First, a transgenic mouse model expressing CUG-repeats identified splicing alterations shared with other mouse models of DM1. Second, using cell cultures from human embryonic muscle, we noted that DM1-associated splicing alterations were significantly enriched in cytoskeleton (e.g. SORBS1, TACC2, TTN, ACTN1 and DMD) and channel (e.g. KCND3 and TRPM4) genes. Third, of the splicing alterations occurring in adult DM1 tissues, one produced a dominant negative variant of the splicing regulator RBFOX1. Notably, half of the splicing events controlled by MBNL1 were co-regulated by RBFOX1, and several events in this category were mis-spliced in DM1 tissues. Our results suggest that reduced RBFOX1 activity in DM1 tissues may amplify several of the splicing alterations caused by the deficiency in MBNL1.",
author = "Roscoe Klinck and Ang{\'e}lique Fourrier and Philippe Thibault and Johanne Toutant and Mathieu Durand and Elvy Lapointe and Caillet-Boudin, {Marie Laure} and Nicolas Sergeant and Genevieve Gourdon and Giovanni Meola and Denis Furling and Jack Puymirat and Benoit Chabot",
year = "2014",
month = "9",
day = "1",
doi = "10.1371/journal.pone.0107324",
language = "English",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

TY - JOUR

T1 - RBFOX1 cooperates with MBNL1 to control splicing in muscle, including events altered in myotonic dystrophy type 1

AU - Klinck, Roscoe

AU - Fourrier, Angélique

AU - Thibault, Philippe

AU - Toutant, Johanne

AU - Durand, Mathieu

AU - Lapointe, Elvy

AU - Caillet-Boudin, Marie Laure

AU - Sergeant, Nicolas

AU - Gourdon, Genevieve

AU - Meola, Giovanni

AU - Furling, Denis

AU - Puymirat, Jack

AU - Chabot, Benoit

PY - 2014/9/1

Y1 - 2014/9/1

N2 - With the goal of identifying splicing alterations in myotonic dystrophy 1 (DM1) tissues that may yield insights into targets or mechanisms, we have surveyed mis-splicing events in three systems using a RT-PCR screening and validation platform. First, a transgenic mouse model expressing CUG-repeats identified splicing alterations shared with other mouse models of DM1. Second, using cell cultures from human embryonic muscle, we noted that DM1-associated splicing alterations were significantly enriched in cytoskeleton (e.g. SORBS1, TACC2, TTN, ACTN1 and DMD) and channel (e.g. KCND3 and TRPM4) genes. Third, of the splicing alterations occurring in adult DM1 tissues, one produced a dominant negative variant of the splicing regulator RBFOX1. Notably, half of the splicing events controlled by MBNL1 were co-regulated by RBFOX1, and several events in this category were mis-spliced in DM1 tissues. Our results suggest that reduced RBFOX1 activity in DM1 tissues may amplify several of the splicing alterations caused by the deficiency in MBNL1.

AB - With the goal of identifying splicing alterations in myotonic dystrophy 1 (DM1) tissues that may yield insights into targets or mechanisms, we have surveyed mis-splicing events in three systems using a RT-PCR screening and validation platform. First, a transgenic mouse model expressing CUG-repeats identified splicing alterations shared with other mouse models of DM1. Second, using cell cultures from human embryonic muscle, we noted that DM1-associated splicing alterations were significantly enriched in cytoskeleton (e.g. SORBS1, TACC2, TTN, ACTN1 and DMD) and channel (e.g. KCND3 and TRPM4) genes. Third, of the splicing alterations occurring in adult DM1 tissues, one produced a dominant negative variant of the splicing regulator RBFOX1. Notably, half of the splicing events controlled by MBNL1 were co-regulated by RBFOX1, and several events in this category were mis-spliced in DM1 tissues. Our results suggest that reduced RBFOX1 activity in DM1 tissues may amplify several of the splicing alterations caused by the deficiency in MBNL1.

UR - http://www.scopus.com/inward/record.url?scp=84922312619&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922312619&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0107324

DO - 10.1371/journal.pone.0107324

M3 - Article

C2 - 25211016

AN - SCOPUS:84922312619

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 9

M1 - e107324

ER -