Neurodegenerative diseases: quantitative predictions of protein-RNA interactions

RNA. 2013 Feb;19(2):129-40. doi: 10.1261/rna.034777.112. Epub 2012 Dec 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Amyloid beta-Protein Precursor / metabolism
  • Aptamers, Nucleotide / metabolism
  • DNA-Binding Proteins / metabolism
  • Female
  • Fragile X Mental Retardation Protein / metabolism
  • Fragile X Syndrome / genetics
  • Fragile X Syndrome / metabolism*
  • Gene Expression Regulation
  • Humans
  • Male
  • Models, Theoretical
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism*
  • Prions / metabolism
  • Protein Binding
  • RNA / metabolism*
  • RNA, Untranslated / metabolism
  • RNA-Binding Proteins / metabolism*
  • Ribonucleoproteins / metabolism*
  • alpha-Synuclein / metabolism

Substances

  • APP protein, human
  • Amyloid beta-Protein Precursor
  • Aptamers, Nucleotide
  • DNA-Binding Proteins
  • Prions
  • RNA, Untranslated
  • RNA-Binding Proteins
  • Ribonucleoproteins
  • alpha-Synuclein
  • Fragile X Mental Retardation Protein
  • RNA