Publications by authors named "D Seoane-Miraz"
miR-107 represses and is sequestered by CUG repeats triggering the MSI2/miR-7 pathogenesis axis in myotonic dystrophy.
Mol Ther Nucleic Acids
September 2025
Myotonic dystrophy type 1 (DM1) is a multisystem genetic disorder characterized by muscle disease, including muscle atrophy partially originating from excessive autophagy. We have previously demonstrated that excessive Musashi-2 (MSI2) repressed the biogenesis of miR-7, which derepressed autophagy, ultimately contributing to muscle atrophy, but the root cause of MSI2 dysregulation is unknown. Herein, we investigate the intricate role of miR-107 in DM1 pathogenesis, focusing on its involvement in the MSI2>miR-7>autophagy axis as this microRNA (miRNA) directly regulates MSI2.
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- - Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease with about a three-year average survival time, primarily characterized by TDP-43 protein issues that affect gene stability and autophagy processes.
- - Research on ALS mice revealed that reducing ATG4B worsens survival and autophagy, while an increase in LC3ylation was observed in both ALS patients and mouse models, suggesting a link between these processes.
- - Antisense oligonucleotides (ASOs) targeting TDP-43 genes have been developed, showing potential for non-invasive treatments that can effectively distribute in the brain after administration.
Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disease caused by a CTG repeat expansion in the gene that generates toxic RNA with a myriad of downstream alterations in RNA metabolism. A key consequence is the sequestration of alternative splicing regulatory proteins MBNL1/2 by expanded transcripts in the affected tissues. MBNL1/2 depletion interferes with a developmental alternative splicing switch that causes the expression of fetal isoforms in adults.
View Article and Find Full Text PDFMyotonic dystrophy type 1 is a debilitating neuromuscular disease causing muscle weakness, myotonia, and cardiac dysfunction. The phenotypes are caused by muscleblind-like (MBNL) protein sequestration by toxic RNA in the DM1 protein kinase () gene. DM1 patients exhibit a pathogenic number of repetitions in , which leads to downstream symptoms.
View Article and Find Full Text PDFMyotonic dystrophy type 1 (DM1) is a rare neuromuscular disease caused by expansion of unstable CTG repeats in a non-coding region of the gene. CUG expansions in mutant transcripts sequester MBNL1 proteins in ribonuclear foci. Depletion of this protein is a primary contributor to disease symptoms such as muscle weakness and atrophy and myotonia, yet upregulation of endogenous MBNL1 levels may compensate for this sequestration.
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