title: Neurodegenerative diseases: quantitative predictions of protein-RNA interactions.
abstract: Increasing evidence indicates that RNA plays an active role in a number of neurodegenerative diseases. We recently introduced a theoretical framework, catRAPID, to predict the binding ability of protein and RNA molecules. Here, we use catRAPID to investigate ribonucleoprotein interactions linked to inherited intellectual disability, amyotrophic lateral sclerosis, Creutzfeuld-Jakob, Alzheimer's, and Parkinson's diseases. We specifically focus on (1) RNA interactions with fragile X mental retardation protein FMRP; (2) protein sequestration caused by CGG repeats; (3) noncoding transcripts regulated by TAR DNA-binding protein 43 TDP-43; (4) autogenous regulation of TDP-43 and FMRP; (5) iron-mediated expression of amyloid precursor protein APP and α-synuclein; (6) interactions between prions and RNA aptamers. Our results are in striking agreement with experimental evidence and provide new insights in processes associated with neuronal function and misfunction.
authors.affiliation: Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain.
authors.forename: Davide
authors.initials: D
authors.lastname: Cirillo
authors.forename: Federico
authors.initials: F
authors.lastname: Agostini
authors.forename: Petr
authors.initials: P
authors.lastname: Klus
authors.forename: Domenica
authors.initials: D
authors.lastname: Marchese
authors.forename: Silvia
authors.initials: S
authors.lastname: Rodriguez
authors.forename: Benedetta
authors.initials: B
authors.lastname: Bolognesi
authors.forename: Gian Gaetano
authors.initials: GG
authors.lastname: Tartaglia
mesh_terms: D000465:Algorithms; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D052157:Aptamers, Nucleotide / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism; D005600:Fragile X Syndrome / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008962:Models, Theoretical; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism*; D011328:Prions / Q000378:metabolism; D011485:Protein Binding; D012313:RNA / Q000378:metabolism*; D022661:RNA, Untranslated / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D052157:Aptamers, Nucleotide; D004268:DNA-Binding Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D011328:Prions; D012313:RNA; D022661:RNA, Untranslated; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D051844:alpha-Synuclein; C545487:APP protein, human