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You are here: Home / Teams / Regulation of Genome Architecture and Dynamics of Splicing (ReGArDS) - D. Auboeuf and C. Bourgeois / Publications / Myotonic dystrophy RNA toxicity alters morphology, adhesion and migration of mouse and human astrocytes

Myotonic dystrophy RNA toxicity alters morphology, adhesion and migration of mouse and human astrocytes

Diana M Dincã, Louison Lallemant, Anchel González-Barriga, Noémie Cresto, Sandra O Braz, Géraldine Sicot, Laure-Elise Pillet, Hélène Polvèche, Paul Magneron, Aline Huguet-Lachon, Hélène Benyamine, Cuauhtli N Azotla-Vilchis, Luis E Agonizantes-Juárez, Julie Tahraoui-Bories, Cécile Martinat, Oscar Hernández-Hernández, Didier Auboeuf, Nathalie Rouach, Cyril F Bourgeois, Geneviève Gourdon, and Mário Gomes-Pereira (2022)

Nat Commun, 13(1):3841.

Brain dysfunction in myotonic dystrophy type 1 (DM1), the prototype of toxic RNAdisorders, has been mainly attributed to neuronal RNA misprocessing, while littleattention has been given to non-neuronal brain cells. Here, using a transgenicmouse model of DM1 that expresses mutant RNA in various brain cell types(neurons, astroglia, and oligodendroglia), we demonstrate that astrocytes exhibitimpaired ramification and polarization in vivo and defects in adhesion,spreading, and migration. RNA-dependent toxicity and phenotypes are also found inhuman transfected glial cells. In line with the cell phenotypes, molecularanalyses reveal extensive expression and accumulation of toxic RNA in astrocytes,which result in RNA spliceopathy that is more severe than in neurons. Astrocytemissplicing affects primarily transcripts that regulate cell adhesion,cytoskeleton, and morphogenesis, and it is confirmed in human brain tissue. Ourfindings demonstrate that DM1 impacts astrocyte cell biology, possiblycompromising their support and regulation of synaptic function.

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