Systematic structure probing experiments (e.g. SHAPE) of RNA mutants such as the mutate-and-map protocol give us a direct access to 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 mutate-and-map experiments, with the evolutionary information available in multiple sequence alignments. We apply neutral theory principles to detect complex long-range dependancies between nucleotides of a single stranded RNA, and implement this technology in 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 and RNA-protein interfaces. aRNhAck is freely available here.