An expanded CTG trinucleotide repeat causes trans RNA interference: a new hypothesis for the pathogenesis of myotonic dystrophy.
Here we report a novel mechanism for the pathogenesis of myotonic dystrophy (DM). The DMPK mRNA with expanded CTG trinucleotide repeats interacts with other transcripts having expanded CAG repeats. This "trans RNA interference" occurs in vitro only when the number of CTG repeats is over 140 and the number of target CAG repeats exceeds 35. The trans RNA interference can explain all the phenomena previously reported about DM.
Sasagawa
N
N
Department of Life Sciences, Graduate School of Arts and Sciences, Tokyo, 153-8902, Japan.
Takahashi
N
N
Suzuki
K
K
Ishiura
S
S
D015894:Genome, Human; D006801:Humans; D009223:Myotonic Dystrophy / Q000235:genetics* / Q000503:physiopathology; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D035362:Transcription Factor TFIID; D019473:Transcription Factors, TFII / Q000235:genetics; D018911:Trinucleotide Repeats / Q000235:genetics*
C585517:DMPK protein, human; D012333:RNA, Messenger; D035362:Transcription Factor TFIID; D019473:Transcription Factors, TFII; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases