Abstract
Dystrophia myotonia type 1 (DM1; Steinert's disease; myotonic dystrophy) is an autosomal dominant disorder due to a large CTG expansion in the 3′-untranslated region (UTR) of the DM protein kinase (DMPK) gene. Transcription of this gene yields a long CUGn-containing mutant (mut) RNA, in which clinical disease is associated with repeats of n=100–5000. Phenomenologically, the expression of mut RNA is correlated with the morphologic observation of ribonucleoprotein precipitates (‘foci’) in the nuclei of DMPK-expressing cells. The prevailing view is that the identification of proteins in these foci is the sine qua non of protein–mut RNA interactions. In this viewpoint, I contend that this is an unwarranted inference that falls short in explaining published data. A new model of mut RNA–protein interactions is proposed with distinct binding properties for soluble and insoluble (focus) mut RNA that accommodate these data without exclusions.
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Acknowledgements
I acknowledge personal communications, thoughtful comments and generous sharing of unpublished data by Drs Thomas Cooper, Yoshihiro Kino, Wlodzimierz Krzyzosiak, Mani Mahadevan, Maurice Swanson and Lubov Timchenko. However, to absolve all of any responsibility for the views expressed in this article, I state that they are solely my own. This paper was presented at the New England Chapter Muscular Dystrophy Association Annual Conference, Rhode Island Hospital, Providence on 30 November 2007. Preparation of this article was supported in part by the Association Française contre les Myopathies.
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Junghans, R. Dystrophia myotonia: why focus on foci?. Eur J Hum Genet 17, 543–553 (2009). https://doi.org/10.1038/ejhg.2008.227
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DOI: https://doi.org/10.1038/ejhg.2008.227
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