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 language | English |
|---|---|
| Article number | e107324 |
| Journal | PLoS One |
| Volume | 9 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sep 1 2014 |
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ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
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 journal › Article
}
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.
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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 -