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Antisense transcription of the myotonic dystrophy locus yields low-abundant RNAs with and without (CAG)n repeat
| Content Provider | Semantic Scholar |
|---|---|
| Author | Gudde, Anke E. E. G. Heeringen, Simon J. Van Oude, Amanda I. De Kessel, Ingeborg D. G. Van Estabrook, Joseph Wang, Eric T. Wieringa, Bé Wansink, Derick G. |
| Copyright Year | 2017 |
| Abstract | The unstable (CTG·CAG)n trinucleotide repeat in the myotonic dystrophy type 1 (DM1) locus is bidirectionally transcribed from genes with terminal overlap. By transcription in the sense direction, the DMPK gene produces various alternatively spliced mRNAs with a (CUG)n repeat in their 3' UTR. Expression in opposite orientation reportedly yields (CAG)n-repeat containing RNA, but both structure and biologic significance of this antisense gene (DM1-AS) are largely unknown. Via a combinatorial approach of computational and experimental analyses of RNA from unaffected individuals and DM1 patients we discovered that DM1-AS spans >6 kb, contains alternative transcription start sites and uses alternative polyadenylation sites up- and downstream of the (CAG)n repeat. Moreover, its primary transcripts undergo alternative splicing, whereby the (CAG)n segment is removed as part of an intron. Thus, in patients a mixture of DM1-AS RNAs with and without expanded (CAG)n repeat are produced. DM1-AS expression appears upregulated in patients, but transcript abundance remains very low in all tissues analyzed. Our data suggest that DM1-AS transcripts belong to the class of long non-coding RNAs. These and other biologically relevant implications for how (CAG)n-expanded transcripts may contribute to DM1 pathology can now be explored experimentally. |
| Starting Page | 1374 |
| Ending Page | 1388 |
| Page Count | 15 |
| File Format | PDF HTM / HTML |
| PubMed reference number | 28102759v1 |
| Alternate Webpage(s) | https://doi.org/10.1080/15476286.2017.1279787 |
| DOI | 10.1080/15476286.2017.1279787 |
| Journal | RNA biology |
| Volume Number | 14 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 3' Untranslated Regions Alternative Splicing Body tissue IGHD1-7 gene Introns MYOTONIC DYSTROPHY 1 Patients Polyadenylation RNA Splicing Transcript Transcription Initiation Site Trinucleotide Repeats Unstable Medical Device Problem antisense therapy biology (field) |
| Content Type | Text |
| Resource Type | Article |
