  Despite the biological importance of non-coding RNA, their structural
characterization remains challenging. Making use of the rapidly growing
sequence databases, we analyze nucleotide coevolution across homologous
sequences via Direct-Coupling Analysis to detect nucleotide-nucleotide
contacts. For a representative set of riboswitches, we show that the results of
Direct-Coupling Analysis in combination with a generalized Nussinov algorithm
systematically improve the results of RNA secondary structure prediction beyond
traditional covariance approaches based on mutual information. Even more
importantly, we show that the results of Direct-Coupling Analysis are enriched
in tertiary structure contacts. By integrating these predictions into molecular
modeling tools, systematically improved tertiary structure predictions can be
obtained, as compared to using secondary structure information alone.
