title: Retrotransposon activation contributes to fragile X premutation rCGG-mediated neurodegeneration.
abstract: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder associated with fragile X premutation carriers. Previous studies have shown that fragile X rCGG repeats are sufficient to cause neurodegeneration and that the rCGG-repeat-binding proteins Pur α and heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 could modulate rCGG-mediated neuronal toxicity. Mobile genetic elements or their remnants populate the genomes, and the activities of these elements are tightly controlled for the fitness of host genomes in different organisms. Here we provide both biochemical and genetic evidence to show that the activation of a specific retrotransposon, gypsy, can modulate rCGG-mediated neurodegeneration in an FXTAS Drosophila model. We find that one of the rCGG-repeat-binding proteins, hnRNP A2/B1, is involved in this process via interaction with heterochromatin protein 1. Knockdown of gypsy RNA by RNAi could suppress the neuronal toxicity caused by rCGG repeats. These data together point to a surprisingly active role for retrotransposition in neurodegeneration.
authors.affiliation: Division of Histology and Embryology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China.
authors.forename: Huiping
authors.initials: H
authors.lastname: Tan
authors.forename: Abrar
authors.initials: A
authors.lastname: Qurashi
authors.forename: Mickael
authors.initials: M
authors.lastname: Poidevin
authors.forename: David L
authors.initials: DL
authors.lastname: Nelson
authors.forename: He
authors.initials: H
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D005123:Eye / Q000254:growth & development / Q000378:metabolism; D005260:Female; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D019636:Neurodegenerative Diseases / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D018626:Retroelements; D019680:Trinucleotide Repeat Expansion
chemical_list: D029721:Drosophila Proteins; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D018626:Retroelements; C439768:hnRNP A2