Abnormal splicing switch of DMD's penultimate exon compromises muscle fibre maintenance in myotonic dystrophy

International audienceMyotonic Dystrophy type 1 (DM1) is a dominant neuromuscular disease caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic RNAs alter the activities of RNA splicing factors resulting in alternative splicing misregulation and muscular dysfunction. Here we show that the abnormal splicing of DMD exon 78 found in dystrophic muscles of DM1 patients is due to the functional loss of MBNL1 and leads to the re-expression of an embryonic dystrophin in place of the adult isoform. Forced expression of embryonic dystrophin in zebrafish using an exon-skipping approach severely impairs the mobility and muscle architecture. Moreover, reproducing Dmd exon 78 missplicing switch in mice induces muscle fibre remodelling and ultrastructural abnormalities including ringed fibres, sarcoplasmic masses or Z-band disorganization, which are characteristic features of dystrophic DM1 skeletal muscles. Thus, we propose that splicing misregulation of DMD exon 78 compromises muscle fibre maintenance and contributes to the progressive dystrophic process in DM

Knowledge of Results and Explicit Instruction: Efficiency of Learning the Crawl Stroke in Swimming

International audienceSpecific verbal instructions when added to simple knowledge of results during learning the crawl stroke by 4 adult novices was followed after 1 mo. of no practice by a higher index of swimming than observed for 4 novices given only the qualitative knowledge of results

First enantioselective total synthesis and configurational assignments of suberosenone and suberosanone as potential antitumor agents

International audienceThe first enantioselective total syntheses of two marine sesquiterpenes (1R)-suberosenone and (1R)-suberosanone are achieved leading to revision of the AC of natural (1S)-suberosanone. Key elements of the synthesis include hyperbaric asymmetric Michael addition and highly efficient silver trifluoroacetate mediated α-alkylation for the formation of ring A

Osteopathia striata with cranial sclerosis: when a fetal malformation syndrome reveals maternal pathology.

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Reversal of RNA toxicity in myotonic dystrophy via a decoy RNA-binding protein with high affinity for expanded CUG repeats

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