Neurodegenerative diseases: quantitative predictions of protein-RNA interactions

Cirillo, Davide; Agostini, Federico, 1985-; Klus, Petr, 1985-; Marchese, Domenica, 1986-; Rodríguez, Silvia; Bolognesi, Benedetta; Tartaglia, Gian Gaetano

doi:http://dx.doi.org/10.1261/rna.034777.112

Neurodegenerative diseases: quantitative predictions of protein-RNA interactions

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Cirillo D, Agostini F, Klus P, Marchese D, Rodriguez S, Bolognesi B et al. Neurodegenerative diseases: quantitative predictions of protein-RNA interactions. RNA. 2013;19(2):129-40. DOI: 10.1261/rna.034777.112

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.