RbFOX1/MBNL1 competition for CCUG RNA repeats binding contributes to myotonic dystrophy type 1/type 2 differences

Chantal Sellier, Estefanía Cerro-Herreros, Markus Blatter, Fernande Freyermuth, Angeline Gaucherot, Frank Ruffenach, Partha Sarkar, Jack Puymirat, Bjarne Udd, John W. Day, Giovanni Meola, Guillaume Bassez, Harutoshi Fujimura, Masanori P. Takahashi, Benedikt Schoser, Denis Furling, Ruben Artero, Frédéric H.T. Allain, Beatriz Llamusi, Nicolas Charlet-Berguerand

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Myotonic dystrophy type 1 and type 2 (DM1, DM2) are caused by expansions of CTG and CCTG repeats, respectively. RNAs containing expanded CUG or CCUG repeats interfere with the metabolism of other RNAs through titration of the Muscleblind-like (MBNL) RNA binding proteins. DM2 follows a more favorable clinical course than DM1, suggesting that specific modifiers may modulate DM severity. Here, we report that the rbFOX1 RNA binding protein binds to expanded CCUG RNA repeats, but not to expanded CUG RNA repeats. Interestingly, rbFOX1 competes with MBNL1 for binding to CCUG expanded repeats and overexpression of rbFOX1 partly releases MBNL1 from sequestration within CCUG RNA foci in DM2 muscle cells. Furthermore, expression of rbFOX1 corrects alternative splicing alterations and rescues muscle atrophy, climbing and flying defects caused by expression of expanded CCUG repeats in a Drosophila model of DM2.

Original languageEnglish (US)
Article number2009
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

Myotonic Dystrophy
RNA
RNA-Binding Proteins
atrophy
proteins
Drosophila
muscle cells
splicing
metabolism
Muscle
muscles
titration
flight
Muscular Atrophy
Alternative Splicing
Titration
expansion
Metabolism
Muscle Cells
defects

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Sellier, C., Cerro-Herreros, E., Blatter, M., Freyermuth, F., Gaucherot, A., Ruffenach, F., ... Charlet-Berguerand, N. (2018). RbFOX1/MBNL1 competition for CCUG RNA repeats binding contributes to myotonic dystrophy type 1/type 2 differences. Nature Communications, 9(1), [2009]. https://doi.org/10.1038/s41467-018-04370-x

RbFOX1/MBNL1 competition for CCUG RNA repeats binding contributes to myotonic dystrophy type 1/type 2 differences. / Sellier, Chantal; Cerro-Herreros, Estefanía; Blatter, Markus; Freyermuth, Fernande; Gaucherot, Angeline; Ruffenach, Frank; Sarkar, Partha; Puymirat, Jack; Udd, Bjarne; Day, John W.; Meola, Giovanni; Bassez, Guillaume; Fujimura, Harutoshi; Takahashi, Masanori P.; Schoser, Benedikt; Furling, Denis; Artero, Ruben; Allain, Frédéric H.T.; Llamusi, Beatriz; Charlet-Berguerand, Nicolas.

In: Nature Communications, Vol. 9, No. 1, 2009, 01.12.2018.

Research output: Contribution to journalArticle

Sellier, C, Cerro-Herreros, E, Blatter, M, Freyermuth, F, Gaucherot, A, Ruffenach, F, Sarkar, P, Puymirat, J, Udd, B, Day, JW, Meola, G, Bassez, G, Fujimura, H, Takahashi, MP, Schoser, B, Furling, D, Artero, R, Allain, FHT, Llamusi, B & Charlet-Berguerand, N 2018, 'RbFOX1/MBNL1 competition for CCUG RNA repeats binding contributes to myotonic dystrophy type 1/type 2 differences', Nature Communications, vol. 9, no. 1, 2009. https://doi.org/10.1038/s41467-018-04370-x
Sellier, Chantal ; Cerro-Herreros, Estefanía ; Blatter, Markus ; Freyermuth, Fernande ; Gaucherot, Angeline ; Ruffenach, Frank ; Sarkar, Partha ; Puymirat, Jack ; Udd, Bjarne ; Day, John W. ; Meola, Giovanni ; Bassez, Guillaume ; Fujimura, Harutoshi ; Takahashi, Masanori P. ; Schoser, Benedikt ; Furling, Denis ; Artero, Ruben ; Allain, Frédéric H.T. ; Llamusi, Beatriz ; Charlet-Berguerand, Nicolas. / RbFOX1/MBNL1 competition for CCUG RNA repeats binding contributes to myotonic dystrophy type 1/type 2 differences. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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