Combining structure probing data on RNA mutants with evolutionary information reveals RNA-binding interfaces

Nucleic Acids Res. 2016 Jun 20;44(11):e104. doi: 10.1093/nar/gkw217. Epub 2016 Apr 19.

Abstract

Systematic structure probing experiments (e.g. SHAPE) of RNA mutants such as the mutate-and-map (MaM) protocol give us a direct access into the genetic robustness of ncRNA structures. Comparative studies of homologous sequences provide a distinct, yet complementary, approach to analyze structural and functional properties of non-coding RNAs. In this paper, we introduce a formal framework to combine the biochemical signal collected from MaM experiments, with the evolutionary information available in multiple sequence alignments. We apply neutral theory principles to detect complex long-range dependencies between nucleotides of a single stranded RNA, and implement these ideas into a software called aRNhAck We illustrate the biological significance of this signal and show that the nucleotides networks calculated with aRNhAck are correlated with nucleotides located in RNA-RNA, RNA-protein, RNA-DNA and RNA-ligand interfaces. aRNhAck is freely available at http://csb.cs.mcgill.ca/arnhack.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Binding Sites
  • Computational Biology / methods
  • DNA / chemistry
  • Evolution, Molecular*
  • Models, Molecular
  • Mutation*
  • Nucleic Acid Conformation*
  • Protein Binding
  • Protein Conformation
  • Proteins / chemistry
  • RNA / chemistry
  • RNA / genetics*
  • Software*
  • Web Browser

Substances

  • Proteins
  • RNA
  • DNA