title: Vulnerability of microRNA biogenesis in FTD-ALS.
abstract: The genetics of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) turn our attention to RNA metabolism, primarily because many of the identified diseases-associated genes encode for RNA-binding proteins. microRNAs (miRNAs) are endogenous noncoding RNAs that play critical roles in maintaining brain integrity. The current review sheds light on miRNA dysregulation in neurodegenerative diseases, focusing on FTD-ALS. We propose that miRNAs are susceptible to fail when protein factors that are critical for miRNA biogenesis malfunction. Accordingly, potential insufficiencies of the 'microprocessor' complex, the nucleo-cytoplasmic export of miRNA precursors or their processing by Dicer were recently reported. Furthermore, specific miRNAs are involved in the regulation of pathways that are essential for neuronal survival or function. Any change in the expression of these specific miRNAs or in their ability to recognize their target sequences will have negative consequences. Taken together, recent reports strengthens the hypothesis that dysregulation of miRNAs might play an important role in the pathogenesis of neurodegenerative diseases, and highlights the miRNA biogenesis machinery as an interesting target for therapeutic interventions for ALS as well as FTD. This article is part of a Special Issue entitled SI:RNA Metabolism in Disease.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Chen
authors.initials: C
authors.lastname: Eitan
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. Electronic address: eran.hornstein@weizmann.ac.il.
authors.forename: Eran
authors.initials: E
authors.lastname: Hornstein
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D057180:Frontotemporal Dementia / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D022022:Nuclear Pore / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D034702:RNA-Binding Protein FUS / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C000599550:FUS protein, human; D035683:MicroRNAs; D034702:RNA-Binding Protein FUS; C000598624:TARDBP protein, human; C408087:DICER1 protein, human; C517918:DROSHA protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: Amyotrophic lateral sclerosis; Dicer; Drosha; Fronto-temporal dementia; MicroRNA; XPO5