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

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.Peer reviewe

In situ observations of the mesophase formation of isotactic polypropylene—A fast time-resolved X-ray diffraction study

In situ observation of the formation process of a mesophase of isotactic polypropylene is reported from a structural point of view. A very rapid transformation from the molten state to the mesophase has, for many years, made in situ observation difficult. In the present study, a rapid temperature jump and high-flux synchrotron radiation X-ray scattering techniques were combined effectively to observe this transformation. Fast time-resolved wide-angle X-ray diffraction during rapid cooling clearly shows the time evolution of the transformation from the molten state to the mesophase. The transformation proceeded very quickly in a narrow temperature range below ca 35 °C. Furthermore, the transformation was accompanied by instantaneous density fluctuations throughout the system, as visualized by microscopic observations. These observations suggest that the mesophase formation proceeds similarly to spinodal decomposition