ETR-3 represses Tau exons 2/3 inclusion, a splicing event abnormally enhanced in myotonic dystrophy type I
✍ Scribed by Olivier Leroy; Claire-Marie Dhaenens; Suzanna Schraen-Maschke; Karim Belarbi; André Delacourte; Athena Andreadis; Bernard Sablonnière; Luc Buée; Nicolas Sergeant; Marie-Laure Caillet-Boudin
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 231 KB
- Volume
- 84
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
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. © 2006 Wiley‐Liss, Inc.