Abstract
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.
Publication types
-
Comparative Study
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Alternative Splicing / physiology*
-
Blotting, Western / methods
-
Brain / metabolism
-
CELF Proteins
-
Cell Line, Tumor
-
Electrophoresis, Polyacrylamide Gel / methods
-
Exons* / physiology
-
Humans
-
Middle Aged
-
Muscle, Skeletal / metabolism
-
Myotonic Dystrophy / genetics*
-
Myotonic Dystrophy / metabolism
-
Nerve Tissue Proteins / physiology*
-
Neuroblastoma
-
Nuclear Proteins / genetics
-
Nuclear Proteins / metabolism
-
RNA, Messenger / metabolism
-
RNA-Binding Proteins / genetics
-
RNA-Binding Proteins / metabolism
-
RNA-Binding Proteins / physiology*
-
Reverse Transcriptase Polymerase Chain Reaction / methods
-
Transfection / methods
-
tau Proteins / genetics
-
tau Proteins / metabolism*
Substances
-
CELF Proteins
-
CELF2 protein, human
-
CELF4 protein, human
-
Nerve Tissue Proteins
-
Nuclear Proteins
-
RNA, Messenger
-
RNA-Binding Proteins
-
tau Proteins