Myotonic dystrophy type 1 (DM1) is a complex multisystemic disorder caused by an expansion of a CTG repeat located at the 3' untranslated region (UTR) of DMPK on chromosome 19q13.3. Aberrant messenger RNA (mRNA) splicing of several genes has been reported to explain some of the symptoms of DM1 including insulin resistance, muscle wasting and myotonia. In this paper we analyzed the expression of the MYH14 mRNA and protein in the muscle of DM1 patients (n=12) with different expansion lengths and normal subjects (n=7). The MYH14 gene is located on chromosome 19q13.3 and encodes for one of the heavy chains of the so called class II "nonmuscle" myosins (NMHCII). MYH14 has two alternative spliced isoforms: the inserted isoform (NMHCII-C1) which includes 8 amino acids located in the globular head of the protein, not encoded by the non inserted isoform (NMHCII-C0). Results showed a splicing unbalance of the MYH14 gene in DM1 muscle, with a prevalent expression of the NMHCII-C0 isoform more marked in DM1 patients harboring large CTG expansions. Minigene assay indicated that levels of the MBNL1 protein positively regulates the inclusion of the MYH14 exon 6. Quantitative analysis of the MYH14 expression revealed a significant reduction in the DM1 muscle samples, both at mRNA and protein level. No differences were found between DM1 and controls in the skeletal muscle localization of MYH14, obtained through immunofluorescence analysis. In line with the thesis of an "RNA gain of function" hypothesis described for the CTG mutation, we conclude that the alterations of the MYH14 gene may contribute to the DM1 molecular pathogenesis.
Rinaldi, F., Terracciano, C., Pisani, V., Massa, R., Loro, E., Vergani, L., et al. (2012). Aberrant splicing and expression of the non muscle myosin heavy-chain gene MYH14 in DM1 muscle tissues. NEUROBIOLOGY OF DISEASE, 45(1), 264-271.
|Tipologia:||Articolo su rivista|
|Citazione:||Rinaldi, F., Terracciano, C., Pisani, V., Massa, R., Loro, E., Vergani, L., et al. (2012). Aberrant splicing and expression of the non muscle myosin heavy-chain gene MYH14 in DM1 muscle tissues. NEUROBIOLOGY OF DISEASE, 45(1), 264-271.|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore MED/03 - Genetica Medica|
|Revisione (peer review):||Esperti anonimi|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.nbd.2011.08.010|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||gen-2012|
|Titolo:||Aberrant splicing and expression of the non muscle myosin heavy-chain gene MYH14 in DM1 muscle tissues|
|Autori:||Rinaldi, F; Terracciano, C; Pisani, V; Massa, R; Loro, E; Vergani, L; Di Girolamo, S; Angelini, C; Gourdon, G; Novelli, G; Botta, A|
|Appare nelle tipologie:||01 - Articolo su rivista|