¹Departments of Surgery and Medicine, Boston University School of Medicine, Roger Williams Medical Center, Providence, RI, USA

Correspondence: Dr RP Junghans, Department of Surgery, Boston University School of Medicine, Roger Williams Medical Center, Providence, RI 02908, USA. Tel: +1 401 456 2507; Fax: +1 401 456 4812; E-mail: rpj@bu.edu

Received 18 July 2007; Revised 8 May 2008; Accepted 16 October 2008; Published online 28 January 2009.

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.