Details

Autor(en) / Beteiligte

• Gudde, Anke E. E. G.
• van Heeringen, Simon J.
• de Oude, Amanda I.
• van Kessel, Ingeborg D. G.
• Estabrook, Joseph
• Wang, Eric T.
• Wieringa, Bé
• Wansink, Derick G.

Titel

Antisense transcription of the myotonic dystrophy locus yields low-abundant RNAs with and without (CAG)n repeat

Ist Teil von

• RNA biology, 2017-10, Vol.14 (10), p.1374-1388

Ort / Verlag

United States: Taylor & Francis

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.