  Non-coding RNAs are ubiquitous, but the discovery of new RNA gene sequences
far outpaces research on their structure and functional interactions. We mine
the evolutionary sequence record to derive precise information about function
and structure of RNAs and RNA-protein complexes. As in protein structure
prediction, we use maximum entropy global probability models of sequence
co-variation to infer evolutionarily constrained nucleotide-nucleotide
interactions within RNA molecules, and nucleotide-amino acid interactions in
RNA-protein complexes. The predicted contacts allow all-atom blinded 3D
structure prediction at good accuracy for several known RNA structures and
RNA-protein complexes. For unknown structures, we predict contacts in 160
non-coding RNA families. Beyond 3D structure prediction, evolutionary couplings
help identify important functional interactions, e.g., at switch points in
riboswitches and at a complex nucleation site in HIV. Aided by accelerating
sequence accumulation, evolutionary coupling analysis can accelerate the
discovery of functional interactions and 3D structures involving RNA.
