ETR-3 represses Tau exons 2/3 inclusion, a splicing event abnormally enhanced in myotonic dystrophy type I.
Altered splicing of transcripts, including the insulin receptor (IR) and the cardiac troponin (cTNT), is a key feature of myotonic dystrophy type I (DM1). CELF and MBNL splicing factor members regulate the splicing of those transcripts. We have previously described an alteration of Tau exon 2 splicing in DM1 brain, resulting in the favored exclusion of exon 2. However, the factors required for alternative splicing of Tau exon 2 remain undetermined. Here we report a decreased expression of CELF family member and MBNL transcripts in DM1 brains as assessed by RT-PCR. By using cellular models with a control- or DM1-like splicing pattern of Tau transcripts, we demonstrate that ETR-3 promotes selectively the exclusion of Tau exon 2. These results together with the analysis of Tau exon 6 and IR exon 11 splicing in brain, muscle, and cell models suggest that DM1 splicing alteration of several transcripts involves various factors.
Leroy
Olivier
O
INSERM U815, Lille, France.
Dhaenens
Claire-Marie
CM
Schraen-Maschke
Suzanna
S
Belarbi
Karim
K
Delacourte
André
A
Andreadis
Athena
A
Sablonnière
Bernard
B
Buée
Luc
L
Sergeant
Nicolas
N
Caillet-Boudin
Marie-Laure
ML
D017398:Alternative Splicing / Q000502:physiology*; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000378:metabolism; D000067878:CELF Proteins; D045744:Cell Line, Tumor; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005091:Exons / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D009223:Myotonic Dystrophy / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009447:Neuroblastoma; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014162:Transfection / Q000379:methods; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D000067878:CELF Proteins; C117363:CELF2 protein, human; C422243:CELF4 protein, human; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D016875:tau Proteins