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Model of RNA pathogenic mechanism in HD.

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posted on 23.02.2012, 01:57 authored by Mónica Bañez-Coronel, Silvia Porta, Birgit Kagerbauer, Elisabet Mateu-Huertas, Lorena Pantano, Isidre Ferrer, Manuel Guzmán, Xavier Estivill, Eulàlia Martí

Several RNA dependent mechanisms contribute to HD pathogenesis. Dicer activity on hairpin-like structures in the mutant HTT gene or in double stranded sense and antisense transcripts induces the formation of sCAG or CAG/CTG siRNA that are incorporated into the RISC complex and trigger abnormal gene silencing. In addition mutant HTT mRNA may induce gene expression deregulation through sequestration of RNA binding proteins that have affinity for CAG repeats, including the transcriptional regulator MBLN. miRNA deregulation produced at least by cellular stress and REST transcriptional malfunction may also contribute to gene expression deregulation in HD.

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