rbFOX1/MBNL1 competition for CCUG RNA repeats binding contributes to myotonic dystrophy type 1/type 2 differences

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Sellier , C , Cerro-Herreros , E , Blatter , M , Freyermuth , F , Gaucherot , A , Ruffenach , F , Sarkar , P , Puymirat , J , Udd , B , Day , J W , Meola , G , Bassez , G , Fujimura , H , Takahashi , M P , Schoser , B , Furling , D , Artero , R , Allain , F H T , 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 , 2009 . https://doi.org/10.1038/s41467-018-04370-x

Title: rbFOX1/MBNL1 competition for CCUG RNA repeats binding contributes to myotonic dystrophy type 1/type 2 differences
Author: Sellier, Chantal; Cerro-Herreros, Estefania; 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, Frederic H. T.; Llamusi, Beatriz; Charlet-Berguerand, Nicolas
Contributor: University of Helsinki, Medicum
Date: 2018-05-22
Language: eng
Number of pages: 15
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/236247
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.
Subject: SPLICING REGULATOR RBFOX2
CONGENITAL HEART-DISEASE
PRE-MESSENGER-RNA
MUSCLEBLIND PROTEINS
SKELETAL-MUSCLE
CHLORIDE CHANNEL
MOLECULAR-BASIS
TRIPLET REPEAT
STEADY-STATE
CUG REPEATS
3111 Biomedicine
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