Dystrophia myotonia: why focus on foci?
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.
Junghans
R P
RP
Departments of Surgery and Medicine, Boston University School of Medicine, Roger Williams Medical Center, Providence, RI 02908, USA. rpj@bu.edu
D000818:Animals; D000067879:CELF1 Protein; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D008954:Models, Biological; D009154:Mutation; D009223:Myotonic Dystrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D065636:Myotonin-Protein Kinase; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018911:Trinucleotide Repeats / Q000235:genetics
D000067879:CELF1 Protein; C102843:CELF1 protein, human; C585517:DMPK protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases