Staufen1s role as a splicing factor and a disease modifier in Myotonic Dystrophy Type I.
In a recent issue ofPLOS Genetics, we reported that the double-stranded RNA-binding protein, Staufen1, functions as a disease modifier in the neuromuscular disorder Myotonic Dystrophy Type I (DM1). In this work, we demonstrated that Staufen1 regulates the alternative splicing of exon 11 of the human Insulin Receptor, a highly studied missplicing event in DM1, through Alu elements located in an intronic region. Furthermore, we found that Staufen1 overexpression regulates numerous alternative splicing events, potentially resulting in both positive and negative effects in DM1. Here, we discuss our major findings and speculate on the details of the mechanisms by which Staufen1 could regulate alternative splicing, in both normal and DM1 conditions. Finally, we highlight the importance of disease modifiers, such as Staufen1, in the DM1 pathology in order to understand the complex disease phenotype and for future development of new therapeutic strategies.
Department of Cellular and Molecular Medicine, University of Ottawa, Center for Neuromuscular Disease , Ottawa, Ontario, Canada.
Emma
E
Bondy-Chorney
Department of Cellular and Molecular Medicine, University of Ottawa, Center for Neuromuscular Disease , Ottawa, Ontario, Canada.
Tara E
TE
Crawford Parks
Department of Cellular and Molecular Medicine, University of Ottawa, Center for Neuromuscular Disease , Ottawa, Ontario, Canada.
Aymeric
A
Ravel-Chapuis
Department of Cellular and Molecular Medicine, University of Ottawa, Center for Neuromuscular Disease , Ottawa, Ontario, Canada.
Bernard J
BJ
Jasmin
Department of Cellular and Molecular Medicine, University of Ottawa, Center for Neuromuscular Disease , Ottawa, Ontario, Canada.
Jocelyn
J
Côté
Alu elements; Myotonic Dystrophy Type I; Stau1-binding sites; Staufen1; alternative splicing; disease modifiers; pre-mRNA splicing
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