Géraldine Sicot

Publications (2)12.3 Total impact

• Article: RNA toxicity in human disease and animal models: From the uncovering of a new mechanism to the development of promising therapies.

  Géraldine Sicot, Mário Gomes-Pereira
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  ABSTRACT: Mutant RNA molecules can be toxic to the cell, causing human disease through trans-acting dominant mechanisms. RNA toxicity was first described in myotonic dystrophy type 1, a multisystemic disorder caused by the abnormal expansion of a non-coding trinucleotide repeat sequence. The development of multiple and complementary animal models of disease has greatly contributed to clarifying the complex disease pathways mediated by toxic RNA molecules. RNA toxicity is not limited to myotonic dystrophy and spreads to an increasing number of human conditions, which share some unifying pathogenic events mediated by toxic RNA accumulation and disruption of RNA-binding proteins. The remarkable progress in the dissection of disease pathobiology resulted in the rational design of molecular therapies, which have been successfully tested in animal models. Toxic RNA diseases, and in particular myotonic dystrophy, clearly illustrate the critical contribution of animal models of disease in translational research: from gene mutation to disease mechanisms, and ultimately to therapy development.
  Biochimica et Biophysica Acta 03/2013; · 4.66 Impact Factor
• Source

  Available from: Mario Gomes-Pereira

  Article: Myotonic dystrophy, when simple repeats reveal complex pathogenic entities: new findings and future challenges.

  Géraldine Sicot, Geneviève Gourdon, Mário Gomes-Pereira
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  ABSTRACT: Expanded, non-coding RNAs can exhibit a deleterious gain-of-function causing human disease through abnormal interactions with RNA-binding proteins. Myotonic dystrophy (DM), the prototypical example of an RNA-dominant disorder, is mediated by trinucleotide repeat-containing transcripts that deregulate alternative splicing. Spliceopathy has therefore been a major focus of DM research. However, changes in gene expression, protein translation and micro-RNA metabolism may also contribute to disease pathology. The exciting finding of bidirectional transcription and non-conventional RNA translation of trinucleotide repeat sequences points to a new scenario, in which DM is not mediated by one single expanded RNA transcript, but involves multiple pathogenic elements and pathways. The study of the growing number of human diseases associated with toxic repeat-containing transcripts provides important insight into the understanding of the complex pathways of RNA toxicity. This review describes some of the recent advances in the understanding of the molecular mechanisms behind DM and other RNA-dominant disorders.
  Human Molecular Genetics 08/2011; 20(R2):R116-23. · 7.64 Impact Factor