Engineering RNA-binding proteins for biology

FEBS J. 2013 Aug;280(16):3734-54. doi: 10.1111/febs.12375. Epub 2013 Jul 5.

Abstract

RNA-binding proteins play essential roles in the regulation of gene expression. Many have modular structures and combine relatively few common domains in various arrangements to recognize RNA sequences and/or structures. Recent progress in engineering the specificity of the PUF class RNA-binding proteins has shown that RNA-binding domains may be combined with various effector or functional domains to regulate the metabolism of targeted RNAs. Designer RNA-binding proteins with tailored sequence specificity will provide valuable tools for biochemical research as well as potential therapeutic applications. In this review, we discuss the suitability of various RNA-binding domains for engineering RNA-binding specificity, based on the structural basis for their recognition. We also compare various protein engineering and design methods applied to RNA-binding proteins, and discuss future applications of these proteins.

Keywords: RNA recognition motif; RNA-binding domains; RNA-binding proteins; computational design; in vitro evolution; phage display; protein engineering; protein-RNA interactions; yeast three-hybrid system; zinc finger.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomedical Research
  • Drug Design
  • Humans
  • Models, Molecular*
  • Protein Engineering*
  • Protein Interaction Domains and Motifs
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • RNA-Binding Proteins / therapeutic use
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / therapeutic use
  • Zinc Fingers

Substances

  • RNA-Binding Proteins
  • Recombinant Fusion Proteins