RBFOX1 cooperates with MBNL1 to control splicing in muscle, including events altered in myotonic dystrophy type 1.
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 i...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4161394?pdf=render |
| _version_ | 1818900012731465728 |
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| author | Roscoe Klinck Angélique Fourrier Philippe Thibault Johanne Toutant Mathieu Durand Elvy Lapointe Marie-Laure Caillet-Boudin Nicolas Sergeant Geneviève Gourdon Giovanni Meola Denis Furling Jack Puymirat Benoit Chabot |
| author_facet | Roscoe Klinck Angélique Fourrier Philippe Thibault Johanne Toutant Mathieu Durand Elvy Lapointe Marie-Laure Caillet-Boudin Nicolas Sergeant Geneviève Gourdon Giovanni Meola Denis Furling Jack Puymirat Benoit Chabot |
| author_sort | Roscoe Klinck |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T19:57:06Z |
| format | Article |
| id | doaj.art-c7092de6f85d46d19bb000179cd70c28 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T19:57:06Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c7092de6f85d46d19bb000179cd70c282022-12-21T20:07:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10732410.1371/journal.pone.0107324RBFOX1 cooperates with MBNL1 to control splicing in muscle, including events altered in myotonic dystrophy type 1.Roscoe KlinckAngélique FourrierPhilippe ThibaultJohanne ToutantMathieu DurandElvy LapointeMarie-Laure Caillet-BoudinNicolas SergeantGeneviève GourdonGiovanni MeolaDenis FurlingJack PuymiratBenoit ChabotWith 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.http://europepmc.org/articles/PMC4161394?pdf=render |
| spellingShingle | Roscoe Klinck Angélique Fourrier Philippe Thibault Johanne Toutant Mathieu Durand Elvy Lapointe Marie-Laure Caillet-Boudin Nicolas Sergeant Geneviève Gourdon Giovanni Meola Denis Furling Jack Puymirat Benoit Chabot RBFOX1 cooperates with MBNL1 to control splicing in muscle, including events altered in myotonic dystrophy type 1. PLoS ONE |
| title | RBFOX1 cooperates with MBNL1 to control splicing in muscle, including events altered in myotonic dystrophy type 1. |
| title_full | RBFOX1 cooperates with MBNL1 to control splicing in muscle, including events altered in myotonic dystrophy type 1. |
| title_fullStr | RBFOX1 cooperates with MBNL1 to control splicing in muscle, including events altered in myotonic dystrophy type 1. |
| title_full_unstemmed | RBFOX1 cooperates with MBNL1 to control splicing in muscle, including events altered in myotonic dystrophy type 1. |
| title_short | RBFOX1 cooperates with MBNL1 to control splicing in muscle, including events altered in myotonic dystrophy type 1. |
| title_sort | rbfox1 cooperates with mbnl1 to control splicing in muscle including events altered in myotonic dystrophy type 1 |
| url | http://europepmc.org/articles/PMC4161394?pdf=render |
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